5-115126738-G-A

Variant names:

• chr5-115126738-G-A
• rs572913711
• NM_001300759.2:c.1916C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001300759.2(TRIM36):​c.1916C>T​(p.Ser639Phe) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S639C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRIM36 NM_001300759.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.53
• Publications: 0 publications found

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]

TRIM36 Gene-Disease associations (from GenCC):

• anencephaly 1

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1822553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM36	NM_001300759.2	c.1916C>T	p.Ser639Phe	missense_variant	Exon 10 of 10	ENST00000513154.6	NP_001287688.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM36	ENST00000513154.6	c.1916C>T	p.Ser639Phe	missense_variant	Exon 10 of 10	2	NM_001300759.2	ENSP00000423934.1
TRIM36	ENST00000282369.7	c.1952C>T	p.Ser651Phe	missense_variant	Exon 10 of 10	1		ENSP00000282369.3
TRIM36	ENST00000514154.1	c.1487C>T	p.Ser496Phe	missense_variant	Exon 9 of 9	1		ENSP00000424259.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1952C>T (p.S651F) alteration is located in exon 10 (coding exon 10) of the TRIM36 gene. This alteration results from a C to T substitution at nucleotide position 1952, causing the serine (S) at amino acid position 651 to be replaced by a phenylalanine (F). 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	0.11
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T;.;T
Eigen	Benign	0.079
Eigen_PC	Benign	0.085
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.81	L;.;.
PhyloP100		2.5
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.5	D;D;D
REVEL	Benign	0.083
Sift	Benign	0.037	D;D;D
Sift4G	Benign	0.37	T;T;T
Polyphen		0.86	P;.;.
Vest4		0.090
MutPred		0.31		Loss of phosphorylation at S651 (P = 0.0452);.;.;
MVP		0.82
MPC		0.19
ClinPred		0.75	D
GERP RS		3.9
Varity_R		0.14
gMVP		0.22
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs572913711; hg19: chr5-114462435;