Variant 5-115126667-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001300759.2(TRIM36):c.1987G>A(p.Gly663Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TRIM36
NM_001300759.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.86

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.1987G>A	p.Gly663Ser	missense_variant	10/10	ENST00000513154.6	NP_001287688.1	Q9NQ86-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRIM36	ENST00000513154.6 linkuse as main transcript	c.1987G>A	p.Gly663Ser	missense_variant	10/10	2	NM_001300759.2	ENSP00000423934.1	Q9NQ86-4
TRIM36	ENST00000282369.7 linkuse as main transcript	c.2023G>A	p.Gly675Ser	missense_variant	10/10	1		ENSP00000282369.3	Q9NQ86-1
TRIM36	ENST00000514154.1 linkuse as main transcript	c.1558G>A	p.Gly520Ser	missense_variant	9/9	1		ENSP00000424259.1	E9PBG3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251178

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2024

The c.2023G>A (p.G675S) alteration is located in exon 10 (coding exon 10) of the TRIM36 gene. This alteration results from a G to A substitution at nucleotide position 2023, causing the glycine (G) at amino acid position 675 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

0.18

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;.;T

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.054

MetaRNN

Uncertain

0.43

T;T;T

MetaSVM

Uncertain

0.15

MutationAssessor

Benign

1.7

L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-4.2

D;D;D

REVEL

Uncertain

0.51

Sift

Uncertain

0.010

D;D;D

Sift4G

Uncertain

0.048

D;D;T

Polyphen

1.0

D;.;.

Vest4

0.31

MutPred

0.49

Loss of stability (P = 0.0387);.;.;

MVP

0.93

MPC

0.13

ClinPred

0.97

GERP RS

5.7

Varity_R

0.53

gMVP

0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over