Genetic Variant ADAP1:p.Thr307Thr (chr7-899208-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_006869.4(ADAP1):c.921G>A(p.Thr307Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00504 in 1,612,652 control chromosomes in the GnomAD database, including 343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.026 ( 174 hom., cov: 34)

Exomes 𝑓: 0.0028 ( 169 hom. )

Consequence

ADAP1
NM_006869.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0790

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 Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 7-899208-C-T is Benign according to our data. Variant chr7-899208-C-T is described in ClinVar as [Benign]. Clinvar id is 776189.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.079 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.089 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAP1	NM_006869.4 link	c.921G>A	p.Thr307Thr	synonymous_variant	Exon 10 of 11	ENST00000265846.10	NP_006860.2	O75689-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAP1	ENST00000265846.10 link	c.921G>A	p.Thr307Thr	synonymous_variant	Exon 10 of 11	1	NM_006869.4	ENSP00000265846.5		O75689-1

Frequencies

GnomAD3 genomes

AF:

0.0265

AC:

4026

AN:

152204

Hom.:

175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00929

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.00679

AC:

1672

AN:

246152

Hom.:

AF XY:

0.00475

AC XY:

638

AN XY:

134436

show subpopulations

Gnomad AFR exome

AF:

0.0950

Gnomad AMR exome

AF:

0.00354

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000453

Gnomad OTH exome

AF:

0.00298

GnomAD4 exome

AF:

0.00281

AC:

4097

AN:

1460330

Hom.:

169

Cov.:

AF XY:

0.00242

AC XY:

1760

AN XY:

726502

show subpopulations

Gnomad4 AFR exome

AF:

0.0944

Gnomad4 AMR exome

AF:

0.00440

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000307

Gnomad4 OTH exome

AF:

0.00588

GnomAD4 genome

AF:

0.0264

AC:

4024

AN:

152322

Hom.:

174

Cov.:

AF XY:

0.0256

AC XY:

1910

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0914

Gnomad4 AMR

AF:

0.00928

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.00717

Hom.:

Bravo

AF:

0.0304

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 18, 2018

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

-0.49

CADD

Benign

8.8

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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