3-96814840-C-T

Variant names:

• chr3-96814840-C-T
• rs868260106
• NM_001080448.3:c.217C>T

Variant summary

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

The NM_001080448.3(EPHA6):​c.217C>T​(p.Gln73*) variant causes a stop gained 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. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EPHA6 NM_001080448.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.856
• 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.217C>T	p.Gln73*	stop_gained	Exon 1 of 18	NP_001073917.2	A0A0B4J1T8
	EPHA6	NM_001278301.2		c.217C>T	p.Gln73*	stop_gained	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.217C>T	p.Gln73*	stop_gained	Exon 1 of 18	ENSP00000374323.5	A0A0B4J1T8
	EPHA6	ENST00000506569.1	TSL:1	c.49C>T	p.Gln17*	stop_gained	Exon 1 of 4	ENSP00000425132.1	H0Y9V0
	EPHA6	ENST00000470610.6	TSL:2	c.217C>T	p.Gln73*	stop_gained	Exon 1 of 5	ENSP00000420598.2	E7EU71

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1425176 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 705760

African (AFR) AF: 0.00 AC: 0 AN: 32450

American (AMR) AF: 0.00 AC: 0 AN: 38404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25576

East Asian (EAS) AF: 0.00 AC: 0 AN: 37450

South Asian (SAS) AF: 0.00 AC: 0 AN: 82322

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1093200

Other (OTH) AF: 0.00 AC: 0 AN: 59172

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	32
DANN	Uncertain	1.0
Eigen	Benign	0.036
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.060	N
PhyloP100		0.86
Vest4		0.74
ClinPred		0.75	D
GERP RS		2.2
PromoterAI		-0.032	Neutral
Mutation Taster		=33/167	disease causing (fs/PTC)

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: rs868260106; hg19: chr3-96533684;