3-96814728-C-T

Variant names:

• chr3-96814728-C-T
• rs759542650
• NM_001080448.3:c.105C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080448.3(EPHA6):​c.105C>T​(p.Cys35Cys) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000281 in 1,424,584 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.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: EPHA6 NM_001080448.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.06
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).

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.105C>T	p.Cys35Cys	synonymous	Exon 1 of 18	NP_001073917.2	A0A0B4J1T8
	EPHA6	NM_001278301.2		c.105C>T	p.Cys35Cys	synonymous	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.105C>T	p.Cys35Cys	synonymous	Exon 1 of 18	ENSP00000374323.5	A0A0B4J1T8
	EPHA6	ENST00000470610.6	TSL:2	c.105C>T	p.Cys35Cys	synonymous	Exon 1 of 5	ENSP00000420598.2	E7EU71
	ENSG00000286447	ENST00000835032.1		n.159+124G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000281 AC: 4 AN: 1424584 Hom.: 0 Cov.: 35 AF XY: 0.00000142 AC XY: 1 AN XY: 705328

African (AFR) AF: 0.00 AC: 0 AN: 32322

American (AMR) AF: 0.00 AC: 0 AN: 40404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23510

East Asian (EAS) AF: 0.00 AC: 0 AN: 39308

South Asian (SAS) AF: 0.00 AC: 0 AN: 81688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5298

European-Non Finnish (NFE) AF: 0.00000366 AC: 4 AN: 1093004

Other (OTH) AF: 0.00 AC: 0 AN: 58508

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	14
DANN	Benign	0.96
PhyloP100		4.1
PromoterAI		0.012	Neutral

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: rs759542650; hg19: chr3-96533572;