rs771049797

Variant names:

• chr3-96814656-C-A
• NM_001080448.3:c.33C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-96814656-C-A
• chr3-96814656-C-G
• chr3-96814656-C-T

Variant summary

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

The NM_001080448.3(EPHA6):​c.33C>A​(p.Ser11Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000756 in 1,323,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: EPHA6 NM_001080448.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220

Genes affected

EPHA6 (HGNC:19296): (EPH receptor A6) Predicted to enable transmembrane-ephrin receptor activity. Predicted to be involved in axon guidance; positive regulation of kinase activity; and transmembrane receptor protein tyrosine kinase signaling pathway. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286447 (HGNC:):

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=0.26499268).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHA6	NM_001080448.3	c.33C>A	p.Ser11Arg	missense_variant	Exon 1 of 18	ENST00000389672.10	NP_001073917.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHA6	ENST00000389672.10	c.33C>A	p.Ser11Arg	missense_variant	Exon 1 of 18	1	NM_001080448.3	ENSP00000374323.5
EPHA6	ENST00000470610.6	c.33C>A	p.Ser11Arg	missense_variant	Exon 1 of 5	2		ENSP00000420598.2
EPHA6	ENST00000506569.1	c.-136C>A		upstream_gene_variant		1		ENSP00000425132.1
ENSG00000286447	ENST00000662485.1	n.-249G>T		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.56e-7 AC: 1 AN: 1323098 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 646540

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: 0.00

Gnomad4 FIN exome AF: 0.0000232

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	.;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.49	T;T
M_CAP	Pathogenic	0.65	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.82	T
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.35	N;N
REVEL	Benign	0.087
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.0	B;.
Vest4		0.33
MutPred		0.16		Loss of phosphorylation at S11 (P = 0.0026);Loss of phosphorylation at S11 (P = 0.0026);
MVP		0.29
MPC		0.29
ClinPred		0.69	D
GERP RS		2.3
gMVP		0.12

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: chr3-96533500;