dbSNP rs71620945: TENM3:c.3863-6A>C (chr4-182753444-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080477.4(TENM3):c.3863-6A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,610,272 control chromosomes in the GnomAD database, including 35,121 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2586 hom., cov: 33)

Exomes 𝑓: 0.20 ( 32535 hom. )

Consequence

TENM3
NM_001080477.4 splice_region, intron

Scores

Splicing: ADA: 0.00007277

Clinical Significance

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

Conservation

PhyloP100: 0.599

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 4-182753444-A-C is Benign according to our data. Variant chr4-182753444-A-C is described in ClinVar as [Benign]. Clinvar id is 257352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4 link	c.3863-6A>C		splice_region_variant, intron_variant	Intron 20 of 27	ENST00000511685.6	NP_001073946.1	Q9P273A0A140VJW8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6 link	c.3863-6A>C		splice_region_variant, intron_variant	Intron 20 of 27	5	NM_001080477.4	ENSP00000424226.1		Q9P273
TENM3	ENST00000502950.1 link	n.2271-6A>C		splice_region_variant, intron_variant	Intron 13 of 14	2

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24791

AN:

152146

Hom.:

2589

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0632

Gnomad AMI

AF:

0.186

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.0354

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.164

GnomAD3 exomes

AF:

0.171

AC:

42410

AN:

247532

Hom.:

4329

AF XY:

0.175

AC XY:

23444

AN XY:

134268

show subpopulations

Gnomad AFR exome

AF:

0.0569

Gnomad AMR exome

AF:

0.124

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.0349

Gnomad SAS exome

AF:

0.121

Gnomad FIN exome

AF:

0.260

Gnomad NFE exome

AF:

0.223

Gnomad OTH exome

AF:

0.179

GnomAD4 exome

AF:

0.204

AC:

297203

AN:

1458008

Hom.:

32535

Cov.:

AF XY:

0.203

AC XY:

146983

AN XY:

725214

show subpopulations

Gnomad4 AFR exome

AF:

0.0574

Gnomad4 AMR exome

AF:

0.126

Gnomad4 ASJ exome

AF:

0.121

Gnomad4 EAS exome

AF:

0.0460

Gnomad4 SAS exome

AF:

0.123

Gnomad4 FIN exome

AF:

0.259

Gnomad4 NFE exome

AF:

0.224

Gnomad4 OTH exome

AF:

0.185

GnomAD4 genome

AF:

0.163

AC:

24783

AN:

152264

Hom.:

2586

Cov.:

AF XY:

0.163

AC XY:

12114

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0631

Gnomad4 AMR

AF:

0.145

Gnomad4 ASJ

AF:

0.117

Gnomad4 EAS

AF:

0.0355

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.272

Gnomad4 NFE

AF:

0.225

Gnomad4 OTH

AF:

0.162

Alfa

AF:

0.197

Hom.:

1712

Bravo

AF:

0.147

Asia WGS

AF:

0.0700

AC:

241

AN:

3478

EpiCase

AF:

0.210

EpiControl

AF:

0.208

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

- -

Aug 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.1

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000073

dbscSNV1_RF

Benign

0.0040

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