chr8-70583299-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_014294.6(TRAM1):c.916G>A(p.Val306Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,613,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

TRAM1
NM_014294.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.295

Publications

3 publications found

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:

ENSG00000298363 (HGNC:):

ENSG00000298363 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022041678).

BP6

Variant 8-70583299-C-T is Benign according to our data. Variant chr8-70583299-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2222834.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAM1	NM_014294.6 link	c.916G>A	p.Val306Ile	missense_variant	Exon 10 of 11	ENST00000262213.7	NP_055109.1	Q15629-1Q6FHL3
TRAM1	NM_001317804.2 link	c.823G>A	p.Val275Ile	missense_variant	Exon 11 of 12		NP_001304733.1	Q15629-2
TRAM1	NM_001317805.2 link	c.658G>A	p.Val220Ile	missense_variant	Exon 10 of 11		NP_001304734.1	Q15629G3XAN4
TRAM1	XM_047421636.1 link	c.658G>A	p.Val220Ile	missense_variant	Exon 11 of 12		XP_047277592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRAM1	ENST00000262213.7 link	c.916G>A	p.Val306Ile	missense_variant	Exon 10 of 11	1	NM_014294.6	ENSP00000262213.2	Q15629-1
TRAM1	ENST00000521425.5 link	c.658G>A	p.Val220Ile	missense_variant	Exon 10 of 11	2		ENSP00000428052.1	G3XAN4
ENSG00000298363	ENST00000755107.1 link	n.675C>T		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000144

AC:

AN:

250672

AF XY:

0.000170

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000969

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000193

AC:

282

AN:

1461344

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

151

AN XY:

726908

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44566

Ashkenazi Jewish (ASJ)

AF:

0.00126

AC:

AN:

26130

East Asian (EAS)

AF:

0.000176

AC:

AN:

39668

South Asian (SAS)

AF:

0.0000813

AC:

AN:

86128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000198

AC:

220

AN:

1111846

Other (OTH)

AF:

0.000199

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000112

AC:

AN:

152092

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3468

East Asian (EAS)

AF:

0.000192

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68006

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000206

Hom.:

Bravo

AF:

0.000121

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000124

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 13, 2021

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.22

.;T

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.15

T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.17

.;N

PhyloP100

0.29

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.22

N;N

REVEL

Benign

0.14

Sift

Benign

0.82

T;T

Sift4G

Benign

0.49

T;T

Polyphen

0.0010

.;B

Vest4

0.16

MVP

0.16

MPC

0.30

ClinPred

0.045

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.017

gMVP

0.50

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr8-70583299-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over