Genetic Variant TRIM64B:p.Ser316Asn (chr11-89871024-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001164397.3(TRIM64B):c.947G>A(p.Ser316Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000054 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIM64B
NM_001164397.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.23

Variant links:

Genes affected

TRIM64B (HGNC:37147): (tripartite motif containing 64B) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TRIM64B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.092249125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM64B	NM_001164397.3 link	c.947G>A	p.Ser316Asn	missense_variant	Exon 7 of 7	ENST00000329862.7	NP_001157869.1	A6NI03
TRIM64B	XM_011542955.3 link	c.521G>A	p.Ser174Asn	missense_variant	Exon 6 of 6		XP_011541257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM64B	ENST00000329862.7 link	c.947G>A	p.Ser316Asn	missense_variant	Exon 7 of 7	1	NM_001164397.3	ENSP00000332969.6		A6NI03

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152154

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000537

AC:

AN:

1396628

Hom.:

Cov.:

AF XY:

0.0000552

AC XY:

AN XY:

688848

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000140

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:

0.0000520

Gnomad4 OTH exome

AF:

0.000208

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000460

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000960

Hom.:

ExAC

AF:

0.0000938

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.947G>A (p.S316N) alteration is located in exon 6 (coding exon 6) of the TRIM64B gene. This alteration results from a G to A substitution at nucleotide position 947, causing the serine (S) at amino acid position 316 to be replaced by an asparagine (N). 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

0.094

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.5

DANN

Benign

0.16

DEOGEN2

Benign

0.00096

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.46

M_CAP

Benign

0.00060

MetaRNN

Benign

0.092

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.45

PROVEAN

Benign

0.28

REVEL

Benign

0.017

Sift

Benign

0.46

Sift4G

Benign

0.57

Vest4

0.10

MutPred

0.30

Gain of catalytic residue at S316 (P = 0.0221);

MVP

0.014

ClinPred

0.015

GERP RS

0.15

Varity_R

0.033

gMVP

0.0074

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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