7-899087-C-A

Variant names:

• chr7-899087-C-A
• rs774777035
• NM_006869.4:c.1042G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006869.4(ADAP1):​c.1042G>T​(p.Val348Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V348M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ADAP1 NM_006869.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

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]

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08937982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAP1	NM_006869.4	c.1042G>T	p.Val348Leu	missense_variant	Exon 10 of 11	ENST00000265846.10	NP_006860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAP1	ENST00000265846.10	c.1042G>T	p.Val348Leu	missense_variant	Exon 10 of 11	1	NM_006869.4	ENSP00000265846.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000409 AC: 1 AN: 244212 Hom.: 0 AF XY: 0.00000751 AC XY: 1 AN XY: 133244

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455886 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724514

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.036	T;.;.;.;T;.;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.91	D;.;D;D;D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.089	T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.030	.;.;.;.;N;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.54	.;N;.;N;N;.;.
REVEL	Benign	0.095
Sift	Benign	0.79	.;T;.;T;T;.;.
Sift4G	Benign	1.0	T;T;T;T;T;.;T
Polyphen		0.0	.;.;.;.;B;.;.
Vest4		0.29
MutPred		0.60		.;.;.;.;Gain of ubiquitination at K353 (P = 0.1375);.;.;
MVP		0.41
MPC		0.37
ClinPred		0.063	T
GERP RS		-2.4
Varity_R		0.053
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs774777035; hg19: chr7-938724;