Variant 3-32818279-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_001039111.3(TRIM71):c.199C>A(p.Arg67Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000631 in 1,426,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000039 ( 0 hom. )

Consequence

TRIM71
NM_001039111.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.23

Variant links:

Genes affected

TRIM71 (HGNC:32669): (tripartite motif containing 71) The protein encoded by this gene is an E3 ubiquitin-protein ligase that binds with miRNAs and maintains the growth and upkeep of embryonic stem cells. This gene also is involved in the G1-S phase transition of the cell cycle. [provided by RefSeq, Dec 2015]

TRIM71 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.872

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM71	NM_001039111.3 linkuse as main transcript	c.199C>A	p.Arg67Ser	missense_variant	1/4	ENST00000383763.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM71	ENST00000383763.6 linkuse as main transcript	c.199C>A	p.Arg67Ser	missense_variant	1/4	1	NM_001039111.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151348

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000392

AC:

AN:

1275096

Hom.:

Cov.:

AF XY:

0.00000319

AC XY:

AN XY:

627130

show subpopulations

Gnomad4 AFR exome

AF:

0.000160

Gnomad4 AMR exome

AF:

0.00

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:

9.66e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151348

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

73898

show subpopulations

Gnomad4 AFR

AF:

0.0000968

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 02, 2023

The c.199C>A (p.R67S) alteration is located in exon 1 (coding exon 1) of the TRIM71 gene. This alteration results from a C to A substitution at nucleotide position 199, causing the arginine (R) at amino acid position 67 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Hydrocephalus, congenital communicating, 1

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

Jan 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.86

M_CAP

Pathogenic

0.98

MetaRNN

Pathogenic

0.87

MetaSVM

Uncertain

0.18

MutationAssessor

Benign

0.90

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.97

PROVEAN

Benign

-0.97

REVEL

Uncertain

0.59

Sift

Benign

0.25

Sift4G

Benign

0.55

Polyphen

0.98

Vest4

0.70

MutPred

0.48

Gain of glycosylation at R67 (P = 0.1298);

MVP

0.76

MPC

1.1

ClinPred

0.90

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

gMVP

0.75

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