Variant chr4-182680694-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001080477.4(TENM3):c.1791T>C(p.Ser597=) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.392

Variant links:

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]

TENM3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TENM3	NM_001080477.4 linkuse as main transcript	c.1791T>C	p.Ser597=	synonymous_variant	10/28	ENST00000511685.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TENM3	ENST00000511685.6 linkuse as main transcript	c.1791T>C	p.Ser597=	synonymous_variant	10/28	5	NM_001080477.4	P1
TENM3	ENST00000502950.1 linkuse as main transcript	n.178T>C		non_coding_transcript_exon_variant	2/15	2
TENM3	ENST00000507737.1 linkuse as main transcript	n.323T>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64604

AN:

151840

Hom.:

14484

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.453

AC:

105879

AN:

233488

Hom.:

26157

AF XY:

0.446

AC XY:

56760

AN XY:

127126

show subpopulations

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 SAS exome

AF:

0.501

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.:

AF XY:

0.397

AC XY:

283854

AN XY:

714826

show subpopulations

Gnomad4 AFR exome

AF:

0.428

Gnomad4 AMR exome

AF:

0.602

Gnomad4 ASJ exome

AF:

0.419

Gnomad4 EAS exome

AF:

0.768

Gnomad4 SAS exome

AF:

0.499

Gnomad4 FIN exome

AF:

0.420

Gnomad4 NFE exome

AF:

0.362

Gnomad4 OTH exome

AF:

0.408

GnomAD4 genome

AF:

0.426

AC:

64682

AN:

151958

Hom.:

14515

Cov.:

AF XY:

0.433

AC XY:

32128

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.434

Gnomad4 AMR

AF:

0.516

Gnomad4 ASJ

AF:

0.429

Gnomad4 EAS

AF:

0.777

Gnomad4 SAS

AF:

0.513

Gnomad4 FIN

AF:

0.424

Gnomad4 NFE

AF:

0.368

Gnomad4 OTH

AF:

0.395

Alfa

AF:

0.386

Hom.:

10052

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

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 22, 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. -

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

-0.52

CADD

Benign

6.9

DANN

Benign

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over