rs377032298

Variant names:

• chr3-96814997-C-A
• rs377032298
• NM_001080448.3:c.374C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-96814997-C-A
• chr3-96814997-C-T

Variant summary

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

The NM_001080448.3(EPHA6):​c.374C>A​(p.Ser125Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000146 in 1,368,134 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S125F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: EPHA6 NM_001080448.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.11
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080448.3. 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
	EPHA6	NM_001080448.3	MANE Select	c.374C>A	p.Ser125Tyr	missense	Exon 1 of 18	NP_001073917.2	A0A0B4J1T8
	EPHA6	NM_001278301.2		c.374C>A	p.Ser125Tyr	missense	Exon 1 of 4	NP_001265230.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA6	ENST00000389672.10	TSL:1 MANE Select	c.374C>A	p.Ser125Tyr	missense	Exon 1 of 18	ENSP00000374323.5	A0A0B4J1T8
	EPHA6	ENST00000506569.1	TSL:1	c.206C>A	p.Ser69Tyr	missense	Exon 1 of 4	ENSP00000425132.1	H0Y9V0
	EPHA6	ENST00000470610.6	TSL:2	c.374C>A	p.Ser125Tyr	missense	Exon 1 of 5	ENSP00000420598.2	E7EU71

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1368134 Hom.: 0 Cov.: 35 AF XY: 0.00000149 AC XY: 1 AN XY: 670992

African (AFR) AF: 0.0000324 AC: 1 AN: 30890

American (AMR) AF: 0.00 AC: 0 AN: 33804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23412

East Asian (EAS) AF: 0.00 AC: 0 AN: 35102

South Asian (SAS) AF: 0.0000133 AC: 1 AN: 75220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5534

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1059652

Other (OTH) AF: 0.00 AC: 0 AN: 56584

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Uncertain	-0.24	T
PhyloP100		4.1
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.18
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.010	D
Polyphen		0.99	D
Vest4		0.63
MVP		0.87
MPC		0.55
ClinPred		0.87	D
GERP RS		4.9
PromoterAI		0.0072	Neutral
gMVP		0.29
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs377032298; hg19: chr3-96533841;