Variant 4-182346733-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001080477.4(TENM3):c.315C>T(p.Leu105=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00722 in 1,613,516 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0067 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0073 ( 51 hom. )

Consequence

TENM3
NM_001080477.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.802

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 4-182346733-C-T is Benign according to our data. Variant chr4-182346733-C-T is described in ClinVar as [Benign]. Clinvar id is 774445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-182346733-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.802 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00667 (1015/152102) while in subpopulation NFE AF= 0.00999 (679/67994). AF 95% confidence interval is 0.00936. There are 5 homozygotes in gnomad4. There are 491 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENM3	NM_001080477.4 linkuse as main transcript	c.315C>T	p.Leu105=	synonymous_variant	3/28	ENST00000511685.6	NP_001073946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TENM3	ENST00000511685.6 linkuse as main transcript	c.315C>T	p.Leu105=	synonymous_variant	3/28	5	NM_001080477.4	ENSP00000424226	P1
TENM3	ENST00000513201.1 linkuse as main transcript	n.565C>T		non_coding_transcript_exon_variant	3/4	1
TENM3	ENST00000512480.5 linkuse as main transcript	c.315C>T	p.Leu105=	synonymous_variant	3/3	3		ENSP00000421320

Frequencies

GnomAD3 genomes

AF:

0.00668

AC:

1015

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00655

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.0126

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00999

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00654

AC:

1627

AN:

248624

Hom.:

AF XY:

0.00659

AC XY:

888

AN XY:

134808

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00468

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00262

Gnomad FIN exome

AF:

0.0124

Gnomad NFE exome

AF:

0.00931

Gnomad OTH exome

AF:

0.00546

GnomAD4 exome

AF:

0.00727

AC:

10629

AN:

1461414

Hom.:

Cov.:

AF XY:

0.00712

AC XY:

5173

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.00517

Gnomad4 ASJ exome

AF:

0.00153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00347

Gnomad4 FIN exome

AF:

0.0126

Gnomad4 NFE exome

AF:

0.00805

Gnomad4 OTH exome

AF:

0.00616

GnomAD4 genome

AF:

0.00667

AC:

1015

AN:

152102

Hom.:

Cov.:

AF XY:

0.00660

AC XY:

491

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00169

Gnomad4 AMR

AF:

0.00654

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.0126

Gnomad4 NFE

AF:

0.00999

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00811

Hom.:

Bravo

AF:

0.00574

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00889

EpiControl

AF:

0.00946

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 23, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2022	TENM3: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

4.0

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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