rs193920907

chr11-5632327-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001003819.4(TRIM6-TRIM34):c.1058G>A(p.Ser353Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 29)
• Consequence: TRIM6-TRIM34 NM_001003819.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.694

Genes affected

TRIM6-TRIM34 (HGNC:):

TRIM34 (HGNC:10063): (tripartite motif containing 34) 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, B-box type 1 and B-box type 2 domain, and a coiled-coil region. Expression of this gene is up-regulated by interferon. This gene is mapped to chromosome 11p15, where it resides within a TRIM gene cluster. Alternative splicing results in multiple transcript variants. A read-through transcript from the upstream TRIM6 gene has also been observed, which results in a fusion product from these neighboring family members. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0474824).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM6-TRIM34	NM_001003819.4	c.1058G>A	p.Ser353Asn	missense_variant	8/14
TRIM34	NM_021616.6	c.-5G>A		5_prime_UTR_variant	2/8	ENST00000429814.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM34	ENST00000429814.3	c.-5G>A		5_prime_UTR_variant	2/8	1	NM_021616.6	P1
TRIM34	ENST00000514226.5	c.-5G>A		5_prime_UTR_variant	2/8	1		P1
TRIM34	ENST00000491385.1	n.47G>A		non_coding_transcript_exon_variant	1/4	1
	ENST00000642298.1	n.330+13358C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 29

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
Cadd	Benign	11
Dann	Benign	0.87
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.032
Sift	Benign	0.18	T
Sift4G	Benign	0.49	T
Polyphen		0.0020	B
Vest4		0.044
MVP		0.30
MPC		0.055
ClinPred		0.031	T
GERP RS		-1.7
gMVP		0.054

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

Other links and lift over

dbSNP: rs193920907; hg19: chr11-5653557; COSMIC: COSV61457829; COSMIC: COSV61457829;