Variant 8-70583662-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014294.6(TRAM1):c.878T>C(p.Val293Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000197 in 152,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Consequence

TRAM1
NM_014294.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.20

Variant links:

Genes affected

TRAM1 (HGNC:20568): (translocation associated membrane protein 1) This gene encodes a multi-pass membrane protein that is part of the mammalian endoplasmic reticulum. The encoded protein influences glycosylation and facilitates the translocation of secretory proteins across the endoplasmic reticulum membrane by regulating which domains of the nascent polypeptide chain are visible to the cytosol during a translocational pause. [provided by RefSeq, Oct 2009]

TRAM1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39065933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRAM1	NM_014294.6 linkuse as main transcript	c.878T>C	p.Val293Ala	missense_variant	9/11	ENST00000262213.7	NP_055109.1
TRAM1	NM_001317804.2 linkuse as main transcript	c.785T>C	p.Val262Ala	missense_variant	10/12		NP_001304733.1
TRAM1	NM_001317805.2 linkuse as main transcript	c.620T>C	p.Val207Ala	missense_variant	9/11		NP_001304734.1
TRAM1	XM_047421636.1 linkuse as main transcript	c.620T>C	p.Val207Ala	missense_variant	10/12		XP_047277592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAM1	ENST00000262213.7 linkuse as main transcript	c.878T>C	p.Val293Ala	missense_variant	9/11	1	NM_014294.6	ENSP00000262213	P1	Q15629-1
TRAM1	ENST00000521425.5 linkuse as main transcript	c.620T>C	p.Val207Ala	missense_variant	9/11	2		ENSP00000428052
TRAM1	ENST00000521049.5 linkuse as main transcript			downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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 20, 2023

The c.878T>C (p.V293A) alteration is located in exon 9 (coding exon 9) of the TRAM1 gene. This alteration results from a T to C substitution at nucleotide position 878, causing the valine (V) at amino acid position 293 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

0.33

BayesDel_addAF

Uncertain

0.095

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

.;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.84

T;D

M_CAP

Benign

0.056

MetaRNN

Benign

0.39

T;T

MetaSVM

Uncertain

0.075

MutationAssessor

Uncertain

2.1

.;M

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.70

N;N

REVEL

Uncertain

0.48

Sift

Benign

0.094

T;T

Sift4G

Benign

0.51

T;T

Polyphen

0.67

.;P

Vest4

0.41

MutPred

0.56

.;Loss of stability (P = 0.0112);

MVP

0.62

MPC

0.92

ClinPred

0.85

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.068

gMVP

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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