chr7-904137-C-G

Variant names:

• chr7-904137-C-G
• NM_006869.4:c.637G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006869.4(ADAP1):​c.637G>C​(p.Glu213Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ADAP1 NM_006869.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35623395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAP1	NM_006869.4	c.637G>C	p.Glu213Gln	missense_variant	Exon 6 of 11	ENST00000265846.10	NP_006860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAP1	ENST00000265846.10	c.637G>C	p.Glu213Gln	missense_variant	Exon 6 of 11	1	NM_006869.4	ENSP00000265846.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.637G>C (p.E213Q) alteration is located in exon 6 (coding exon 6) of the ADAP1 gene. This alteration results from a G to C substitution at nucleotide position 637, causing the glutamic acid (E) at amino acid position 213 to be replaced by a glutamine (Q). 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	0.23
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.37	T;.;.;.;D;.;.
Eigen	Benign	0.071
Eigen_PC	Benign	0.012
FATHMM_MKL	Benign	0.72	D
LIST_S2	Pathogenic	0.99	D;.;D;D;D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.36	T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Pathogenic	3.1	.;.;.;.;M;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.5	.;N;.;D;D;.;.
REVEL	Benign	0.12
Sift	Uncertain	0.0060	.;D;.;D;D;.;.
Sift4G	Benign	0.080	T;T;T;T;T;.;D
Polyphen		0.81	.;.;.;.;P;.;.
Vest4		0.70
MutPred		0.44		.;.;.;.;Loss of ubiquitination at K216 (P = 0.1388);Loss of ubiquitination at K216 (P = 0.1388);.;
MVP		0.40
MPC		0.40
ClinPred		0.91	D
GERP RS		4.3
Varity_R		0.56
gMVP		0.42

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.

Other links and lift over

hg19: chr7-943774;