6-30189170-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_003449.5(TRIM26):c.934A>T(p.Thr312Ser) 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. 12/21 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, TRIM26
• BP4: Computational evidence support a benign effect (MetaRNN=0.15060428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM26	NM_003449.5	c.934A>T	p.Thr312Ser	missense_variant	9/10	ENST00000454678.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM26	ENST00000454678.7	c.934A>T	p.Thr312Ser	missense_variant	9/10	1	NM_003449.5	P1
TRIM26	ENST00000437089.5	c.934A>T	p.Thr312Ser	missense_variant	8/9	1		P1
TRIM26	ENST00000453195.5	c.934A>T	p.Thr312Ser	missense_variant	8/9	1		P1
TRIM26	ENST00000480999.1	n.1007A>T		non_coding_transcript_exon_variant	2/3	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

May 11, 2022

The c.934A>T (p.T312S) alteration is located in exon 9 (coding exon 6) of the TRIM26 gene. This alteration results from a A to T substitution at nucleotide position 934, causing the threonine (T) at amino acid position 312 to be replaced by a serine (S). 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	0.25
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0084	T;T;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.38	N;N;N
MutationTaster	Benign	0.96	N;N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.17	N;N;N
REVEL	Benign	0.082
Sift	Benign	0.64	T;T;T
Sift4G	Benign	0.18	T;T;T
Polyphen		0.91	P;P;P
Vest4		0.20
MutPred		0.34		Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);
MVP		0.23
MPC		1.3
ClinPred		0.83	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.076
gMVP		0.53

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.

Other links and lift over

hg19: chr6-30156947;