Variant chr15-83122777-T-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_023003.5(TM6SF1):c.502T>G(p.Cys168Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TM6SF1
NM_023003.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.70

Variant links:

Genes affected

TM6SF1 (HGNC:11860): (transmembrane 6 superfamily member 1) Predicted to be integral component of membrane. Predicted to be active in lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

TM6SF1 links:

HDGFL3 (HGNC:24937): (HDGF like 3) Predicted to enable double-stranded DNA binding activity; microtubule binding activity; and transcription coregulator activity. Predicted to be involved in several processes, including microtubule polymerization; negative regulation of microtubule depolymerization; and neuron projection development. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

HDGFL3 links:

TM6SF1 (HGNC:):

TM6SF1 links:

Genome browser will be placed here

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=0.20554066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TM6SF1	NM_023003.5 linkuse as main transcript	c.502T>G	p.Cys168Gly	missense_variant	6/10	ENST00000322019.14	NP_075379.2	Q9BZW5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TM6SF1	ENST00000322019.14 linkuse as main transcript	c.502T>G	p.Cys168Gly	missense_variant	6/10	1	NM_023003.5	ENSP00000317000.9		Q9BZW5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461740

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2024

The c.502T>G (p.C168G) alteration is located in exon 6 (coding exon 6) of the TM6SF1 gene. This alteration results from a T to G substitution at nucleotide position 502, causing the cysteine (C) at amino acid position 168 to be replaced by a glycine (G). 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

0.14

BayesDel_addAF

Uncertain

0.038

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.032

T;.;T

Eigen

Benign

-0.015

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.98

L;L;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.0050

B;.;.

Vest4

0.46

MutPred

0.48

Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);.;

MVP

0.27

MPC

0.34

ClinPred

0.38

GERP RS

6.2

Varity_R

0.31

gMVP

0.38

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