6-30196680-C-T

Position:

• chr6-30196680-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_003449.5(TRIM26):​c.601G>A​(p.Glu201Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TRIM26 NM_003449.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.81

Genes affected

TRIM26 (HGNC:12962): (tripartite motif containing 26) 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 protein localizes to cytoplasmic bodies. Although the function of the protein is unknown, the RING domain suggests that the protein may have DNA-binding activity. The gene localizes to the major histocompatibility complex (MHC) class I region on chromosome 6. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jun 2011]

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=0.11562538).
• BP6: Variant 6-30196680-C-T is Benign according to our data. Variant chr6-30196680-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3328674.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM26	NM_003449.5	c.601G>A	p.Glu201Lys	missense_variant	6/10	ENST00000454678.7	NP_003440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM26	ENST00000454678.7	c.601G>A	p.Glu201Lys	missense_variant	6/10	1	NM_003449.5	ENSP00000410446.2
TRIM26	ENST00000437089.5	c.601G>A	p.Glu201Lys	missense_variant	5/9	1		ENSP00000395491.1
TRIM26	ENST00000453195.5	c.601G>A	p.Glu201Lys	missense_variant	5/9	1		ENSP00000391879.1
TRIM26	ENST00000416596.5	c.601G>A	p.Glu201Lys	missense_variant	6/6	5		ENSP00000413673.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461866 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727232

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 30, 2024

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	0.090
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T;T;T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.061
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.83	.;.;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;L;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.7	N;N;N;D
REVEL	Benign	0.066
Sift	Benign	0.30	T;T;T;T
Sift4G	Benign	0.19	T;T;T;.
Polyphen		0.10	B;B;B;.
Vest4		0.15
MutPred		0.46		Gain of ubiquitination at E201 (P = 0.0101);Gain of ubiquitination at E201 (P = 0.0101);Gain of ubiquitination at E201 (P = 0.0101);Gain of ubiquitination at E201 (P = 0.0101);
MVP		0.19
MPC		1.0
ClinPred		0.64	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.039
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-30164457;