rs12268910

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016824.5(ADD3):c.717+16T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,608,486 control chromosomes in the GnomAD database, including 60,748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 14498 hom., cov: 32)

Exomes 𝑓: 0.22 ( 46250 hom. )

Consequence

ADD3
NM_016824.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.00900

Publications

12 publications found

Variant links:

Genes affected

ADD3 (HGNC:245): (adducin 3) Adducins are heteromeric proteins composed of different subunits referred to as adducin alpha, beta and gamma. The three subunits are encoded by distinct genes and belong to a family of membrane skeletal proteins involved in the assembly of spectrin-actin network in erythrocytes and at sites of cell-cell contact in epithelial tissues. While adducins alpha and gamma are ubiquitously expressed, the expression of adducin beta is restricted to brain and hematopoietic tissues. Adducin, originally purified from human erythrocytes, was found to be a heterodimer of adducins alpha and beta. Polymorphisms resulting in amino acid substitutions in these two subunits have been associated with the regulation of blood pressure in an animal model of hypertension. Heterodimers consisting of alpha and gamma subunits have also been described. Structurally, each subunit is comprised of two distinct domains. The amino-terminal region is protease resistant and globular in shape, while the carboxy-terminal region is protease sensitive. The latter contains multiple phosphorylation sites for protein kinase C, the binding site for calmodulin, and is required for association with spectrin and actin. Alternatively spliced adducin gamma transcripts encoding different isoforms have been described. The functions of the different isoforms are not known. [provided by RefSeq, Jul 2008]

ADD3 Gene-Disease associations (from GenCC):

cerebral palsy, spastic quadriplegic, 3
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
complex neurodevelopmental disorder with motor features
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
spastic quadriplegic cerebral palsy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ADD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 10-110118752-T-G is Benign according to our data. Variant chr10-110118752-T-G is described in ClinVar as Benign. ClinVar VariationId is 1164946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016824.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADD3	NM_016824.5	MANE Select	c.717+16T>G	intron	N/A	NP_058432.1	Q9UEY8-1
ADD3	NM_001320591.2		c.717+16T>G	intron	N/A	NP_001307520.1	Q9UEY8-1
ADD3	NM_001320592.2		c.717+16T>G	intron	N/A	NP_001307521.1	Q9UEY8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADD3	ENST00000356080.9	TSL:1 MANE Select	c.717+16T>G	intron	N/A	ENSP00000348381.4	Q9UEY8-1
ADD3	ENST00000277900.12	TSL:1	c.717+16T>G	intron	N/A	ENSP00000277900.8	Q9UEY8-2
ADD3	ENST00000360162.7	TSL:1	c.717+16T>G	intron	N/A	ENSP00000353286.3	Q9UEY8-2

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

53800

AN:

151974

Hom.:

14452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.745

Gnomad AMI

AF:

0.132

Gnomad AMR

AF:

0.210

Gnomad ASJ

AF:

0.231

Gnomad EAS

AF:

0.407

Gnomad SAS

AF:

0.526

Gnomad FIN

AF:

0.148

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.317

GnomAD2 exomes

AF:

0.269

AC:

66780

AN:

248622

AF XY:

0.275

show subpopulations

Gnomad AFR exome

AF:

0.753

Gnomad AMR exome

AF:

0.125

Gnomad ASJ exome

AF:

0.238

Gnomad EAS exome

AF:

0.398

Gnomad FIN exome

AF:

0.154

Gnomad NFE exome

AF:

0.180

Gnomad OTH exome

AF:

0.224

GnomAD4 exome

AF:

0.216

AC:

314697

AN:

1456394

Hom.:

46250

Cov.:

AF XY:

0.224

AC XY:

162143

AN XY:

724004

show subpopulations

African (AFR)

AF:

0.767

AC:

25566

AN:

33354

American (AMR)

AF:

0.134

AC:

5947

AN:

44514

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

6063

AN:

26056

East Asian (EAS)

AF:

0.412

AC:

16302

AN:

39584

South Asian (SAS)

AF:

0.514

AC:

44175

AN:

85994

European-Finnish (FIN)

AF:

0.150

AC:

7968

AN:

53258

Middle Eastern (MID)

AF:

0.335

AC:

1923

AN:

5738

European-Non Finnish (NFE)

AF:

0.172

AC:

191069

AN:

1107744

Other (OTH)

AF:

0.261

AC:

15684

AN:

60152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

10101

20201

30302

40402

50503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7168

14336

21504

28672

35840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.354

AC:

53909

AN:

152092

Hom.:

14498

Cov.:

AF XY:

0.354

AC XY:

26327

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.745

AC:

30913

AN:

41474

American (AMR)

AF:

0.209

AC:

3200

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

800

AN:

3468

East Asian (EAS)

AF:

0.407

AC:

2107

AN:

5176

South Asian (SAS)

AF:

0.525

AC:

2534

AN:

4824

European-Finnish (FIN)

AF:

0.148

AC:

1572

AN:

10596

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.175

AC:

11905

AN:

67960

Other (OTH)

AF:

0.319

AC:

674

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1275

2550

3826

5101

6376

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.276

Hom.:

2051

Bravo

AF:

0.369

Asia WGS

AF:

0.493

AC:

1713

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.0

(source)

DANN

Benign

0.45

PhyloP100

0.0090

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over