Variant 15-83136614-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000322019.14(TM6SF1):c.1055G>A(p.Arg352His) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,459,896 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

TM6SF1
ENST00000322019.14 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.34

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TM6SF1	NM_023003.5 linkuse as main transcript	c.1055G>A	p.Arg352His	missense_variant	10/10	ENST00000322019.14	NP_075379.2	Q9BZW5-1
HDGFL3	NM_016073.4 linkuse as main transcript	c.*2656C>T		3_prime_UTR_variant	6/6	ENST00000299633.7	NP_057157.1	Q9Y3E1A0A024R216

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TM6SF1	ENST00000322019.14 linkuse as main transcript	c.1055G>A	p.Arg352His	missense_variant	10/10	1	NM_023003.5	ENSP00000317000.9		Q9BZW5-1
HDGFL3	ENST00000299633.7 linkuse as main transcript	c.*2656C>T		3_prime_UTR_variant	6/6	1	NM_016073.4	ENSP00000299633.4		Q9Y3E1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

248676

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134314

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1459896

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726188

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

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:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

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

Dec 14, 2021

The c.1055G>A (p.R352H) alteration is located in exon 10 (coding exon 10) of the TM6SF1 gene. This alteration results from a G to A substitution at nucleotide position 1055, causing the arginine (R) at amino acid position 352 to be replaced by a histidine (H). 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

0.20

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.31

T;.

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.066

MetaRNN

Uncertain

0.47

T;T

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.8

M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.5

D;D

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.46

MutPred

0.81

Gain of ubiquitination at K356 (P = 0.1128);.;

MVP

0.28

MPC

0.72

ClinPred

0.97

GERP RS

5.5

Varity_R

0.73

gMVP

0.93

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