Variant 7-935380-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000265846.10(ADAP1):c.208G>A(p.Val70Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,406,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

ADAP1
ENST00000265846.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.05

Variant links:

Genes affected

ADAP1 (HGNC:16486): (ArfGAP with dual PH domains 1) Enables GTPase activator activity. Involved in regulation of GTPase activity. Located in cytosol; nucleus; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ADAP1 links:

COX19 (HGNC:28074): (cytochrome c oxidase assembly factor COX19) COX19 encodes a cytochrome c oxidase (COX)-assembly protein. The S. cerevisiae Cox19 protein may play a role in metal transport to the mitochondrial intermembrane space and assembly of complex IV of the mitochondrial respiratory chain (Sacconi et al., 2005 [PubMed 16212937]).[supplied by OMIM, Mar 2008]

COX19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37700018).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADAP1	NM_006869.4 linkuse as main transcript	c.208G>A	p.Val70Met	missense_variant	2/11	ENST00000265846.10	NP_006860.2
ADAP1	NM_001284308.2 linkuse as main transcript	c.241G>A	p.Val81Met	missense_variant	2/11		NP_001271237.2
ADAP1	NM_001284309.2 linkuse as main transcript	c.-9G>A		5_prime_UTR_variant	2/11		NP_001271238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAP1	ENST00000265846.10 linkuse as main transcript	c.208G>A	p.Val70Met	missense_variant	2/11	1	NM_006869.4	ENSP00000265846	P1	O75689-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.11e-7

AC:

AN:

1406618

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

694722

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.23e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2023

The c.208G>A (p.V70M) alteration is located in exon 2 (coding exon 2) of the ADAP1 gene. This alteration results from a G to A substitution at nucleotide position 208, causing the valine (V) at amino acid position 70 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

.;T;.;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.38

T;T;T;T

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.2

.;M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.4

N;N;.;N

REVEL

Benign

0.22

Sift

Uncertain

0.0050

D;D;.;D

Sift4G

Uncertain

0.020

D;D;.;.

Polyphen

0.89

.;P;.;.

Vest4

0.62

MutPred

0.51

.;Gain of disorder (P = 0.0562);Gain of disorder (P = 0.0562);.;

MVP

0.46

MPC

0.88

ClinPred

0.96

GERP RS

4.1

Varity_R

0.49

gMVP

0.54

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over