Variant chr8-27287753-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000305364.9(TRIM35):c.1279C>T(p.Arg427Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,610,140 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

TRIM35
ENST00000305364.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.55

Variant links:

Genes affected

TRIM35 (HGNC:16285): (tripartite motif containing 35) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The function of this protein has not been identified. [provided by RefSeq, Jul 2008]

TRIM35 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=0.29879054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM35	NM_171982.5 linkuse as main transcript	c.1279C>T	p.Arg427Cys	missense_variant	6/6	ENST00000305364.9	NP_741983.2	Q9UPQ4-1
TRIM35	XM_047421602.1 linkuse as main transcript	c.829C>T	p.Arg277Cys	missense_variant	6/6		XP_047277558.1
TRIM35	NM_001362813.2 linkuse as main transcript	c.*359C>T		3_prime_UTR_variant	5/5		NP_001349742.1
TRIM35	NM_001304495.2 linkuse as main transcript	c.*359C>T		3_prime_UTR_variant	4/4		NP_001291424.1	E5RGB3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRIM35	ENST00000305364.9 linkuse as main transcript	c.1279C>T	p.Arg427Cys	missense_variant	6/6	1	NM_171982.5	ENSP00000301924.4	Q9UPQ4-1
TRIM35	ENST00000521253.1 linkuse as main transcript	c.*359C>T		3_prime_UTR_variant	4/4	1		ENSP00000428770.1	E5RGB3
TRIM35	ENST00000521283.1 linkuse as main transcript	c.288+283C>T		intron_variant		2		ENSP00000429356.1	H0YBF3

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000231

AC:

AN:

238504

Hom.:

AF XY:

0.000310

AC XY:

AN XY:

129212

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000150

Gnomad ASJ exome

AF:

0.000103

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00119

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000747

Gnomad OTH exome

AF:

0.00104

GnomAD4 exome

AF:

0.000141

AC:

205

AN:

1457816

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

128

AN XY:

724934

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000159

Gnomad4 ASJ exome

AF:

0.0000386

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000983

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000702

Gnomad4 OTH exome

AF:

0.000316

GnomAD4 genome

AF:

0.000112

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.0000907

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000280

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Feb 05, 2024

The c.1279C>T (p.R427C) alteration is located in exon 6 (coding exon 6) of the TRIM35 gene. This alteration results from a C to T substitution at nucleotide position 1279, causing the arginine (R) at amino acid position 427 to be replaced by a cysteine (C). 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

0.23

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.30

MetaSVM

Uncertain

-0.012

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-5.0

REVEL

Uncertain

0.63

Sift

Pathogenic

0.0

Sift4G

Benign

0.092

Polyphen

1.0

Vest4

0.68

MutPred

0.69

Gain of catalytic residue at L428 (P = 0.0133);

MVP

0.84

MPC

1.3

ClinPred

0.38

GERP RS

5.3

Varity_R

0.54

gMVP

0.76

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