chr5-115130626-A-G

Position:

• chr5-115130626-A-G

Variant summary

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

The NM_001300759.2(TRIM36):​c.1762T>C​(p.Trp588Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM36 NM_001300759.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.99

Genes affected

TRIM36 (HGNC:16280): (tripartite motif containing 36) 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. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM36	NM_001300759.2	c.1762T>C	p.Trp588Arg	missense_variant	9/10	ENST00000513154.6	NP_001287688.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM36	ENST00000513154.6	c.1762T>C	p.Trp588Arg	missense_variant	9/10	2	NM_001300759.2	ENSP00000423934.1
TRIM36	ENST00000282369.7	c.1798T>C	p.Trp600Arg	missense_variant	9/10	1		ENSP00000282369.3
TRIM36	ENST00000514154.1	c.1333T>C	p.Trp445Arg	missense_variant	8/9	1		ENSP00000424259.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Oct 20, 2024

The c.1798T>C (p.W600R) alteration is located in exon 9 (coding exon 9) of the TRIM36 gene. This alteration results from a T to C substitution at nucleotide position 1798, causing the tryptophan (W) at amino acid position 600 to be replaced by an arginine (R). 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	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.57	D;D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.3	M;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-7.9	D;D;D
REVEL	Uncertain	0.45
Sift	Benign	0.095	T;T;T
Sift4G	Benign	0.16	T;T;T
Polyphen		0.92	P;.;.
Vest4		0.66
MutPred		0.51		Gain of disorder (P = 0.0149);.;.;
MVP		0.84
MPC		0.38
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.76
gMVP		0.79

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: chr5-114466323;