dbSNP rs556239318: ATAD3A:p.Gly13Gly (chr1-1512307-T-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS1

The NM_001170535.3(ATAD3A):c.39T>A(p.Gly13Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000189 in 1,255,354 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00097 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

ATAD3A
NM_001170535.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.675

Publications

0 publications found

Variant links:

Genes affected

ATAD3A (HGNC:25567): (ATPase family AAA domain containing 3A) This gene encodes a ubiquitously expressed mitochondrial membrane protein that contributes to mitochondrial dynamics, nucleoid organization, protein translation, cell growth, and cholesterol metabolism. This gene is a member of the ATPase family AAA-domain containing 3 gene family which, in humans, includes two other paralogs. Naturally occurring mutations in this gene are associated with distinct neurological syndromes including Harel-Yoon syndrome. High-level expression of this gene is associated with poor survival in breast cancer patients. A homozygous knockout of the orthologous gene in mice results in embryonic lethality at day 7.5 due to growth retardation and defective development of the trophoblast lineage. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ATAD3A Gene-Disease associations (from GenCC):

Harel-Yoon syndrome
Inheritance: AR, AD, SD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)
pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ATAD3A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-1512307-T-A is Benign according to our data. Variant chr1-1512307-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2638020.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.675 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000972 (146/150244) while in subpopulation AFR AF = 0.00334 (137/40958). AF 95% confidence interval is 0.00289. There are 1 homozygotes in GnomAd4. There are 64 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170535.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATAD3A	NM_001170535.3	MANE Select	c.39T>A	p.Gly13Gly	synonymous	Exon 1 of 16	NP_001164006.1	Q9NVI7-2
ATAD3A	NM_018188.5		c.39T>A	p.Gly13Gly	synonymous	Exon 1 of 16	NP_060658.3
ATAD3A	NM_001170536.3		c.-416T>A		upstream_gene	N/A	NP_001164007.1	Q9NVI7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATAD3A	ENST00000378756.8	TSL:1 MANE Select	c.39T>A	p.Gly13Gly	synonymous	Exon 1 of 16	ENSP00000368031.3	Q9NVI7-2
ATAD3A	ENST00000378755.9	TSL:2	c.39T>A	p.Gly13Gly	synonymous	Exon 1 of 16	ENSP00000368030.5	Q9NVI7-1
ATAD3A	ENST00000936382.1		c.39T>A	p.Gly13Gly	synonymous	Exon 1 of 16	ENSP00000606441.1

Frequencies

GnomAD3 genomes

AF:

0.000966

AC:

145

AN:

150146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00333

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000462

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000966

GnomAD2 exomes

AF:

0.000406

AC:

AN:

29530

AF XY:

0.000299

show subpopulations

Gnomad AFR exome

AF:

0.00789

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00259

GnomAD4 exome

AF:

0.0000823

AC:

AN:

1105110

Hom.:

Cov.:

AF XY:

0.0000876

AC XY:

AN XY:

525352

show subpopulations

African (AFR)

AF:

0.00306

AC:

AN:

23176

American (AMR)

AF:

0.000390

AC:

AN:

10258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14180

East Asian (EAS)

AF:

0.00

AC:

AN:

26734

South Asian (SAS)

AF:

0.00

AC:

AN:

21724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34018

Middle Eastern (MID)

AF:

0.000344

AC:

AN:

2910

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

928328

Other (OTH)

AF:

0.000343

AC:

AN:

43782

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000972

AC:

146

AN:

150244

Hom.:

Cov.:

AF XY:

0.000872

AC XY:

AN XY:

73382

show subpopulations

African (AFR)

AF:

0.00334

AC:

137

AN:

40958

American (AMR)

AF:

0.000461

AC:

AN:

15180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5030

South Asian (SAS)

AF:

0.00

AC:

AN:

4742

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67286

Other (OTH)

AF:

0.000956

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000971

Hom.:

Bravo

AF:

0.00115

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.4

(source)

DANN

Benign

0.68

PhyloP100

-0.68

PromoterAI

-0.010

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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