rs373432052

Variant names:

• chr3-96814837-A-C
• NM_001080448.3:c.214A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-96814837-A-C
• chr3-96814837-A-G
• chr3-96814837-A-T

Variant summary

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

The NM_001080448.3(EPHA6):​c.214A>C​(p.Thr72Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. 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. T72A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: EPHA6 NM_001080448.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.595

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]

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=0.08207458).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHA6	NM_001080448.3	c.214A>C	p.Thr72Pro	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.214A>C	p.Thr72Pro	missense_variant	Exon 1 of 18	1	NM_001080448.3	ENSP00000374323.5
EPHA6	ENST00000506569.1	c.46A>C	p.Thr16Pro	missense_variant	Exon 1 of 4	1		ENSP00000425132.1
EPHA6	ENST00000470610.6	c.214A>C	p.Thr72Pro	missense_variant	Exon 1 of 5	2		ENSP00000420598.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424544 Hom.: 0 Cov.: 35 AF XY: 0.00000142 AC XY: 1 AN XY: 705396

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: 0.00

Gnomad4 NFE exome AF: 9.15e-7

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	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	3.2
DANN	Benign	0.81
DEOGEN2	Benign	0.018	.;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.30	T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.082	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.18	N;N
REVEL	Benign	0.057
Sift	Benign	0.23	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.0	B;.
Vest4		0.18
MutPred		0.080		Gain of catalytic residue at P71 (P = 0.0119);Gain of catalytic residue at P71 (P = 0.0119);
MVP		0.47
MPC		0.33
ClinPred		0.038	T
GERP RS		-2.4
gMVP		0.041

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: chr3-96533681;