Variant 4-182324243-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080477.4(TENM3):c.223A>G(p.Thr75Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TENM3
NM_001080477.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.959

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.092867285).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENM3	NM_001080477.4 link	c.223A>G	p.Thr75Ala	missense_variant	2/28	ENST00000511685.6	NP_001073946.1	Q9P273A0A140VJW8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TENM3	ENST00000511685.6 link	c.223A>G	p.Thr75Ala	missense_variant	2/28	5	NM_001080477.4	ENSP00000424226.1	Q9P273
TENM3	ENST00000513201.1 link	n.473A>G		non_coding_transcript_exon_variant	2/4	1
TENM3	ENST00000512480.5 link	c.223A>G	p.Thr75Ala	missense_variant	2/3	3		ENSP00000421320.1	D6RGC5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460222

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726552

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.223A>G (p.T75A) alteration is located in exon 1 (coding exon 1) of the TENM3 gene. This alteration results from a A to G substitution at nucleotide position 223, causing the threonine (T) at amino acid position 75 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.056

.;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.51

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.36

T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.093

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

.;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.72

N;N

REVEL

Benign

0.029

Sift

Benign

0.52

T;T

Sift4G

Benign

0.86

T;T

Polyphen

0.010

B;B

Vest4

0.20

MutPred

0.42

Gain of glycosylation at T75 (P = 0.0733);Gain of glycosylation at T75 (P = 0.0733);

MVP

0.043

MPC

0.57

ClinPred

0.061

GERP RS

-2.0

Varity_R

0.038

gMVP

0.32

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