6-30186247-C-T

Position:

• chr6-30186247-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003449.5(TRIM26):​c.1249G>A​(p.Glu417Lys) 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. 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: 31)
• Consequence: TRIM26 NM_003449.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.50

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 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=0.14676648).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM26	NM_003449.5	c.1249G>A	p.Glu417Lys	missense_variant	10/10	ENST00000454678.7	NP_003440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM26	ENST00000454678.7	c.1249G>A	p.Glu417Lys	missense_variant	10/10	1	NM_003449.5	ENSP00000410446.2
TRIM26	ENST00000437089.5	c.1249G>A	p.Glu417Lys	missense_variant	9/9	1		ENSP00000395491.1
TRIM26	ENST00000453195.5	c.1249G>A	p.Glu417Lys	missense_variant	9/9	1		ENSP00000391879.1
TRIM26	ENST00000480999.1	n.1322G>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.1249G>A (p.E417K) alteration is located in exon 10 (coding exon 7) of the TRIM26 gene. This alteration results from a G to A substitution at nucleotide position 1249, causing the glutamic acid (E) at amino acid position 417 to be replaced by a lysine (K). 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	0.21
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0063	T;T;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.83	.;.;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N;N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.43	N;N;N
REVEL	Benign	0.18
Sift	Benign	0.56	T;T;T
Sift4G	Uncertain	0.049	D;D;D
Polyphen		0.61	P;P;P
Vest4		0.24
MutPred		0.44		Gain of sheet (P = 4e-04);Gain of sheet (P = 4e-04);Gain of sheet (P = 4e-04);
MVP		0.45
MPC		0.93
ClinPred		0.22	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.091
gMVP		0.80

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: chr6-30154024;