Variant chr8-27287862-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000305364.9(TRIM35):c.1170C>A(p.His390Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TRIM35
ENST00000305364.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.713

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08102691).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM35	NM_171982.5 linkuse as main transcript	c.1170C>A	p.His390Gln	missense_variant	6/6	ENST00000305364.9	NP_741983.2	Q9UPQ4-1
TRIM35	XM_047421602.1 linkuse as main transcript	c.720C>A	p.His240Gln	missense_variant	6/6		XP_047277558.1
TRIM35	NM_001362813.2 linkuse as main transcript	c.*250C>A		3_prime_UTR_variant	5/5		NP_001349742.1
TRIM35	NM_001304495.2 linkuse as main transcript	c.*250C>A		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.1170C>A	p.His390Gln	missense_variant	6/6	1	NM_171982.5	ENSP00000301924.4	Q9UPQ4-1
TRIM35	ENST00000521253.1 linkuse as main transcript	c.*250C>A		3_prime_UTR_variant	4/4	1		ENSP00000428770.1	E5RGB3
TRIM35	ENST00000521283.1 linkuse as main transcript	c.288+174C>A		intron_variant		2		ENSP00000429356.1	H0YBF3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460840

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726754

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 28, 2023

The c.1170C>A (p.H390Q) alteration is located in exon 6 (coding exon 6) of the TRIM35 gene. This alteration results from a C to A substitution at nucleotide position 1170, causing the histidine (H) at amino acid position 390 to be replaced by a glutamine (Q). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.034

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.54

M_CAP

Benign

0.058

MetaRNN

Benign

0.081

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.5

REVEL

Benign

0.060

Sift

Benign

0.29

Sift4G

Benign

0.27

Polyphen

0.018

Vest4

0.22

MutPred

0.43

Gain of sheet (P = 0.1208);

MVP

0.42

MPC

0.68

ClinPred

0.20

GERP RS

-3.0

Varity_R

0.062

gMVP

0.55

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over