Genetic Variant NM_016824.5:c.717+16T>G (chr10-110118752-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADD3	NM_016824.5 link	c.717+16T>G		intron_variant	Intron 6 of 14	ENST00000356080.9	NP_058432.1	Q9UEY8-1Q5VU08

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADD3	ENST00000356080.9 link	c.717+16T>G		intron_variant	Intron 6 of 14	1	NM_016824.5	ENSP00000348381.4		Q9UEY8-1

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

GnomAD3 exomes

AF:

0.269

AC:

66780

AN:

248622

Hom.:

13260

AF XY:

0.275

AC XY:

36989

AN XY:

134262

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 SAS exome

AF:

0.522

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

Gnomad4 AFR exome

AF:

0.767

Gnomad4 AMR exome

AF:

0.134

Gnomad4 ASJ exome

AF:

0.233

Gnomad4 EAS exome

AF:

0.412

Gnomad4 SAS exome

AF:

0.514

Gnomad4 FIN exome

AF:

0.150

Gnomad4 NFE exome

AF:

0.172

Gnomad4 OTH exome

AF:

0.261

GnomAD4 genome

AF:

0.354

AC:

53909

AN:

152092

Hom.:

14498

Cov.:

AF XY:

0.354

AC XY:

26327

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.745

Gnomad4 AMR

AF:

0.209

Gnomad4 ASJ

AF:

0.231

Gnomad4 EAS

AF:

0.407

Gnomad4 SAS

AF:

0.525

Gnomad4 FIN

AF:

0.148

Gnomad4 NFE

AF:

0.175

Gnomad4 OTH

AF:

0.319

Alfa

AF:

0.265

Hom.:

1822

Bravo

AF:

0.369

Asia WGS

AF:

0.493

AC:

1713

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.0

DANN

Benign

0.45

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over