rs17263582

chr4-182753544-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001080477.4(TENM3):c.3957C>T(p.Gly1319=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,612,446 control chromosomes in the GnomAD database, including 36,452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2765 hom., cov: 33)
  • Exomes 𝑓: 0.21 (33687 hom.)
• Consequence: TENM3 NM_001080477.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.505

Genes affected

TENM3 (HGNC:29944): (teneurin transmembrane protein 3) This gene encodes a member of the teneurin transmembrane protein family. The encoded protein may be involved in the regulation of neuronal development including development of the visual pathway. Mutations in this gene have been associated with microphthalmia and developmental dysplasia of the hip. [provided by RefSeq, Jan 2023]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 4-182753544-C-T is Benign according to our data. Variant chr4-182753544-C-T is described in ClinVar as [Benign]. Clinvar id is 257353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.505 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENM3	NM_001080477.4	c.3957C>T	p.Gly1319=	synonymous_variant	21/28	ENST00000511685.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM3	ENST00000511685.6	c.3957C>T	p.Gly1319=	synonymous_variant	21/28	5	NM_001080477.4	P1
TENM3	ENST00000502950.1	n.2365C>T		non_coding_transcript_exon_variant	14/15	2

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27406 AN: 152022 Hom.: 2765 Cov.: 33

Gnomad AFR AF: 0.0881

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.225

GnomAD3 exomes AF: 0.197 AC: 49053 AN: 248714 Hom.: 5274 AF XY: 0.203 AC XY: 27445 AN XY: 134932

Gnomad AFR exome AF: 0.0862

Gnomad AMR exome AF: 0.133

Gnomad ASJ exome AF: 0.242

Gnomad EAS exome AF: 0.178

Gnomad SAS exome AF: 0.201

Gnomad FIN exome AF: 0.224

Gnomad NFE exome AF: 0.224

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.212 AC: 309513 AN: 1460306 Hom.: 33687 Cov.: 34 AF XY: 0.212 AC XY: 154277 AN XY: 726420

Gnomad4 AFR exome AF: 0.0875

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.253

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.203

Gnomad4 FIN exome AF: 0.222

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.213

GnomAD4 genome AF: 0.180 AC: 27418 AN: 152140 Hom.: 2765 Cov.: 33 AF XY: 0.182 AC XY: 13521 AN XY: 74388

Gnomad4 AFR AF: 0.0880

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.225

Alfa AF: 0.201 Hom.: 2513

Bravo AF: 0.174

Asia WGS AF: 0.182 AC: 632 AN: 3478

EpiCase AF: 0.225

EpiControl AF: 0.238

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Microphthalmia, isolated, with coloboma 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	5.1
Dann	Benign	0.53

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

LitVar

Other links and lift over

dbSNP: rs17263582; hg19: chr4-183674697; COSMIC: COSV69306274;