7-899087-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006869.4(ADAP1):​c.1042G>A​(p.Val348Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ADAP1 NM_006869.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08992192).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006869.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAP1	NM_006869.4	MANE Select	c.1042G>A	p.Val348Met	missense	Exon 10 of 11	NP_006860.2	O75689-1
	ADAP1	NM_001284308.2		c.1075G>A	p.Val359Met	missense	Exon 10 of 11	NP_001271237.2	O75689-2
	ADAP1	NM_001284309.2		c.826G>A	p.Val276Met	missense	Exon 10 of 11	NP_001271238.2	O75689-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAP1	ENST00000265846.10	TSL:1 MANE Select	c.1042G>A	p.Val348Met	missense	Exon 10 of 11	ENSP00000265846.5	O75689-1
	ADAP1	ENST00000539900.5	TSL:2	c.1075G>A	p.Val359Met	missense	Exon 10 of 11	ENSP00000442682.1	O75689-2
	ADAP1	ENST00000943017.1		c.1060G>A	p.Val354Met	missense	Exon 10 of 11	ENSP00000613076.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455888 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 724516

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000447 AC: 2 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111900

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000936 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.34	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.86	N
PhyloP100		1.6
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.050
Sift	Benign	0.49	T
Sift4G	Benign	0.70	T
Polyphen		0.0070	B
Vest4		0.26
MutPred		0.62		Gain of catalytic residue at V348 (P = 0.0053)
MVP		0.38
MPC		0.39
ClinPred		0.21	T
GERP RS		-2.4
Varity_R		0.039
gMVP		0.49
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs774777035; hg19: chr7-938724;