chr3-96814839-C-T

Variant names:

• chr3-96814839-C-T
• rs77729199
• NM_001080448.3:c.216C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001080448.3(EPHA6):​c.216C>T​(p.Thr72Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,578,330 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (46 hom., cov: 31)
  • Exomes 𝑓: 0.0019 (51 hom.)
• Consequence: EPHA6 NM_001080448.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.758
• Publications: 2 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.076).
• BP6: Variant 3-96814839-C-T is Benign according to our data. Variant chr3-96814839-C-T is described in ClinVar as Benign. ClinVar VariationId is 778089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.758 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0134 (2035/152162) while in subpopulation AFR AF = 0.0442 (1834/41536). AF 95% confidence interval is 0.0425. There are 46 homozygotes in GnomAd4. There are 932 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2035 AD gene.

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.216C>T	p.Thr72Thr	synonymous	Exon 1 of 18	NP_001073917.2	A0A0B4J1T8
	EPHA6	NM_001278301.2		c.216C>T	p.Thr72Thr	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.216C>T	p.Thr72Thr	synonymous	Exon 1 of 18	ENSP00000374323.5	A0A0B4J1T8
	EPHA6	ENST00000506569.1	TSL:1	c.48C>T	p.Thr16Thr	synonymous	Exon 1 of 4	ENSP00000425132.1	H0Y9V0
	EPHA6	ENST00000470610.6	TSL:2	c.216C>T	p.Thr72Thr	synonymous	Exon 1 of 5	ENSP00000420598.2	E7EU71

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 2027 AN: 152044 Hom.: 46 Cov.: 31

Gnomad AFR AF: 0.0441

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0143

GnomAD2 exomes AF: 0.00406 AC: 763 AN: 187906 AF XY: 0.00334

Gnomad AFR exome AF: 0.0407

Gnomad AMR exome AF: 0.00359

Gnomad ASJ exome AF: 0.0213

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000452

Gnomad OTH exome AF: 0.00318

GnomAD4 exome AF: 0.00190 AC: 2715 AN: 1426168 Hom.: 51 Cov.: 35 AF XY: 0.00175 AC XY: 1237 AN XY: 706362

African (AFR) AF: 0.0461 AC: 1496 AN: 32472

American (AMR) AF: 0.00441 AC: 170 AN: 38556

Ashkenazi Jewish (ASJ) AF: 0.0194 AC: 496 AN: 25592

East Asian (EAS) AF: 0.00 AC: 0 AN: 37520

South Asian (SAS) AF: 0.000158 AC: 13 AN: 82456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50934

Middle Eastern (MID) AF: 0.00349 AC: 20 AN: 5728

European-Non Finnish (NFE) AF: 0.000202 AC: 221 AN: 1093688

Other (OTH) AF: 0.00505 AC: 299 AN: 59222

GnomAD4 genome AF: 0.0134 AC: 2035 AN: 152162 Hom.: 46 Cov.: 31 AF XY: 0.0125 AC XY: 932 AN XY: 74394

African (AFR) AF: 0.0442 AC: 1834 AN: 41536

American (AMR) AF: 0.00516 AC: 79 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5108

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 67994

Other (OTH) AF: 0.0142 AC: 30 AN: 2114

Alfa AF: 0.00681 Hom.: 21

Bravo AF: 0.0148

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.1
DANN	Benign	0.66
PhyloP100		-0.76
PromoterAI		-0.050	Neutral
Mutation Taster		=300/0	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: rs77729199; hg19: chr3-96533683;