chr4-182680694-T-C

Variant names:

• chr4-182680694-T-C
• rs2871328
• NM_001080477.4:c.1791T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001080477.4(TENM3):​c.1791T>C​(p.Ser597Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 1,592,062 control chromosomes in the GnomAD database, including 131,795 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14515 hom., cov: 31)
  • Exomes 𝑓: 0.39 (117280 hom.)
• Consequence: TENM3 NM_001080477.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.392

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 4-182680694-T-C is Benign according to our data. Variant chr4-182680694-T-C is described in ClinVar as [Benign]. Clinvar id is 257347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.392 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4	c.1791T>C	p.Ser597Ser	synonymous_variant	Exon 10 of 28	ENST00000511685.6	NP_001073946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6	c.1791T>C	p.Ser597Ser	synonymous_variant	Exon 10 of 28	5	NM_001080477.4	ENSP00000424226.1
TENM3	ENST00000502950.1	n.178T>C		non_coding_transcript_exon_variant	Exon 2 of 15	2
TENM3	ENST00000507737.1	n.323T>C		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64604 AN: 151840 Hom.: 14484 Cov.: 31

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.393

GnomAD2 exomes AF: 0.453 AC: 105879 AN: 233488 AF XY: 0.446

Gnomad AFR exome AF: 0.425

Gnomad AMR exome AF: 0.618

Gnomad ASJ exome AF: 0.425

Gnomad EAS exome AF: 0.792

Gnomad FIN exome AF: 0.419

Gnomad NFE exome AF: 0.358

Gnomad OTH exome AF: 0.422

GnomAD4 exome AF: 0.394 AC: 567317 AN: 1440104 Hom.: 117280 Cov.: 36 AF XY: 0.397 AC XY: 283854 AN XY: 714826

Gnomad4 AFR exome AF: 0.428 AC: 13818 AN: 32304

Gnomad4 AMR exome AF: 0.602 AC: 23433 AN: 38956

Gnomad4 ASJ exome AF: 0.419 AC: 10580 AN: 25266

Gnomad4 EAS exome AF: 0.768 AC: 30265 AN: 39404

Gnomad4 SAS exome AF: 0.499 AC: 41683 AN: 83460

Gnomad4 FIN exome AF: 0.420 AC: 22334 AN: 53228

Gnomad4 NFE exome AF: 0.362 AC: 399100 AN: 1102350

Gnomad4 Remaining exome AF: 0.408 AC: 24266 AN: 59434

GnomAD4 genome AF: 0.426 AC: 64682 AN: 151958 Hom.: 14515 Cov.: 31 AF XY: 0.433 AC XY: 32128 AN XY: 74262

Gnomad4 AFR AF: 0.434 AC: 0.434153 AN: 0.434153

Gnomad4 AMR AF: 0.516 AC: 0.516102 AN: 0.516102

Gnomad4 ASJ AF: 0.429 AC: 0.429025 AN: 0.429025

Gnomad4 EAS AF: 0.777 AC: 0.776612 AN: 0.776612

Gnomad4 SAS AF: 0.513 AC: 0.512714 AN: 0.512714

Gnomad4 FIN AF: 0.424 AC: 0.423878 AN: 0.423878

Gnomad4 NFE AF: 0.368 AC: 0.368244 AN: 0.368244

Gnomad4 OTH AF: 0.395 AC: 0.394886 AN: 0.394886

Alfa AF: 0.386 Hom.: 10672

Bravo AF: 0.432

Asia WGS AF: 0.638 AC: 2220 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Microphthalmia, isolated, with coloboma 9 Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.9
DANN	Benign	0.74
Mutation Taster		=100/0	polymorphism (auto)

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: rs2871328; hg19: chr4-183601847; COSMIC: COSV108246382;