Genetic Variant ENST00000371130.7:c.7959C>G (chrX-124380755-G-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The ENST00000371130.7(TENM1):c.7959C>G(p.Arg2653Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R2653R) has been classified as Benign.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000027 ( 0 hom. 3 hem. )

Failed GnomAD Quality Control

Consequence

TENM1
ENST00000371130.7 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.52

Variant links:

Genes affected

TENM1 (HGNC:8117): (teneurin transmembrane protein 1) The protein encoded by this gene belongs to the tenascin family and teneurin subfamily. It is expressed in the neurons and may function as a cellular signal transducer. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

TENM1 links:

STAG2 (HGNC:11355): (STAG2 cohesin complex component) The protein encoded by this gene is a subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Targeted inactivation of this gene results in chromatid cohesion defects and aneuploidy, suggesting that genetic disruption of cohesin is a cause of aneuploidy in human cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

STAG2 links:

LOC105373331 (HGNC:):

LOC105373331 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP7

Synonymous conserved (PhyloP=-2.52 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
TENM1	NM_001163278.2 link	c.7980C>G	p.Arg2660Arg	synonymous_variant	Exon 35 of 35	NP_001156750.1	Q9UKZ4-2
TENM1	NM_001163279.1 link	c.7977C>G	p.Arg2659Arg	synonymous_variant	Exon 32 of 32	NP_001156751.1	Q9UKZ4B7ZMH4
TENM1	NM_014253.3 link	c.7959C>G	p.Arg2653Arg	synonymous_variant	Exon 31 of 31	NP_055068.2	Q9UKZ4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
TENM1	ENST00000371130.7 link	c.7959C>G	p.Arg2653Arg	synonymous_variant	Exon 31 of 31	1	ENSP00000360171.3	Q9UKZ4-1
TENM1	ENST00000422452.3 link	c.7926C>G	p.Arg2642Arg	synonymous_variant	Exon 35 of 35	1	ENSP00000403954.4	A0A8Z5AZJ6
STAG2	ENST00000469481.1 link	n.454-31067G>C		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000548

AC:

AN:

182469

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

67173

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000527

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000273

AC:

AN:

1097615

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

363025

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000370

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0080

DANN

Benign

0.63

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over