chr7-905132-G-C

Position:

• chr7-905132-G-C

Variant summary

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

The NM_006869.4(ADAP1):​c.429C>G​(p.Asn143Lys) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAP1 NM_006869.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.518

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]

ADAP1 (HGNC:):

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=0.26378417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAP1	NM_006869.4	c.429C>G	p.Asn143Lys	missense_variant	5/11	ENST00000265846.10	NP_006860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAP1	ENST00000265846.10	c.429C>G	p.Asn143Lys	missense_variant	5/11	1	NM_006869.4	ENSP00000265846.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2024

The c.429C>G (p.N143K) alteration is located in exon 5 (coding exon 5) of the ADAP1 gene. This alteration results from a C to G substitution at nucleotide position 429, causing the asparagine (N) at amino acid position 143 to be replaced by a lysine (K). 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	Pathogenic	0.92
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.20	T;.;.;.;D;.;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.92	D;.;D;D;D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.26	T;T;T;T;T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.4	.;.;.;.;M;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-4.8	.;D;.;D;D;.;D
REVEL	Benign	0.15
Sift	Benign	0.045	.;D;.;T;D;.;T
Sift4G	Uncertain	0.054	T;T;T;T;T;.;.
Polyphen		0.98	.;.;.;.;D;.;.
Vest4		0.76
MutPred		0.48		.;.;.;.;Loss of ubiquitination at K138 (P = 0.0318);Loss of ubiquitination at K138 (P = 0.0318);.;
MVP		0.33
MPC		0.47
ClinPred		0.89	D
GERP RS		-0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.74
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr7-944769;