8-70594568-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014294.6(TRAM1):c.508A>G(p.Ile170Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000294 in 1,598,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

TRAM1
NM_014294.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.49

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.124887645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAM1	NM_014294.6 link	c.508A>G	p.Ile170Val	missense_variant	Exon 6 of 11	ENST00000262213.7	NP_055109.1	Q15629-1Q6FHL3
TRAM1	NM_001317804.2 link	c.415A>G	p.Ile139Val	missense_variant	Exon 7 of 12		NP_001304733.1	Q15629-2
TRAM1	NM_001317805.2 link	c.250A>G	p.Ile84Val	missense_variant	Exon 6 of 11		NP_001304734.1	Q15629G3XAN4
TRAM1	XM_047421636.1 link	c.250A>G	p.Ile84Val	missense_variant	Exon 7 of 12		XP_047277592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRAM1	ENST00000262213.7 link	c.508A>G	p.Ile170Val	missense_variant	Exon 6 of 11	1	NM_014294.6	ENSP00000262213.2	Q15629-1
TRAM1	ENST00000521425.5 link	c.250A>G	p.Ile84Val	missense_variant	Exon 6 of 11	2		ENSP00000428052.1	G3XAN4
TRAM1	ENST00000520700.1 link	n.475A>G		non_coding_transcript_exon_variant	Exon 6 of 6	5
TRAM1	ENST00000521049.5 link	n.444+3327A>G		intron_variant	Intron 3 of 6	5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

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

GnomAD2 exomes

AF:

0.0000796

AC:

AN:

238544

AF XY:

0.0000620

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000602

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000304

AC:

AN:

1446728

Hom.:

Cov.:

AF XY:

0.0000347

AC XY:

AN XY:

719426

show subpopulations

African (AFR)

AF:

0.0000307

AC:

AN:

32560

American (AMR)

AF:

0.000562

AC:

AN:

42720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25682

East Asian (EAS)

AF:

0.000359

AC:

AN:

39022

South Asian (SAS)

AF:

0.00

AC:

AN:

83158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53012

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00000452

AC:

AN:

1105244

Other (OTH)

AF:

0.00

AC:

AN:

59632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41404

American (AMR)

AF:

0.0000655

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000192

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68010

Other (OTH)

AF:

0.00

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:

0.0000200

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 13, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.508A>G (p.I170V) alteration is located in exon 6 (coding exon 6) of the TRAM1 gene. This alteration results from a A to G substitution at nucleotide position 508, causing the isoleucine (I) at amino acid position 170 to be replaced by a valine (V). 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

0.078

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

.;T

Eigen

Benign

0.027

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.12

T;T

MetaSVM

Uncertain

-0.16

MutationAssessor

Benign

1.7

.;L

PhyloP100

3.5

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.85

N;N

REVEL

Uncertain

0.34

Sift

Benign

0.065

T;T

Sift4G

Benign

0.094

T;T

Polyphen

0.17

.;B

Vest4

0.32

MVP

0.22

MPC

0.34

ClinPred

0.099

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.27

Mutation Taster

=70/30

polymorphism

(source)

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

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

8-70594568-T-C

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