Variant 11-10514927-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016422.4(RNF141):c.682C>T(p.His228Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RNF141
NM_016422.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.75

Variant links:

Genes affected

RNF141 (HGNC:21159): (ring finger protein 141) The protein encoded by this gene contains a RING finger, a motif known to be involved in protein-DNA and protein-protein interactions. Abundant expression of this gene was found in the testicular tissue of fertile men, but was not detected in azoospermic patients. Studies of the mouse counterpart suggest that this gene may function as a testis specific transcription factor during spermatogenesis. [provided by RefSeq, Jul 2008]

RNF141 links:

RNF141 (HGNC:):

RNF141 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18194735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF141	NM_016422.4 linkuse as main transcript	c.682C>T	p.His228Tyr	missense_variant	6/6	ENST00000265981.7	NP_057506.2	Q8WVD5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF141	ENST00000265981.7 linkuse as main transcript	c.682C>T	p.His228Tyr	missense_variant	6/6	1	NM_016422.4	ENSP00000265981.2		Q8WVD5-1
RNF141	ENST00000534281.1 linkuse as main transcript	n.2814C>T		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460144

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726388

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Apr 09, 2024

The c.682C>T (p.H228Y) alteration is located in exon 6 (coding exon 5) of the RNF141 gene. This alteration results from a C to T substitution at nucleotide position 682, causing the histidine (H) at amino acid position 228 to be replaced by a tyrosine (Y). 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

0.010

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.028

Eigen

Benign

0.012

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0095

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.5

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.68

REVEL

Benign

0.11

Sift

Benign

0.33

Sift4G

Benign

0.24

Polyphen

0.15

Vest4

0.22

MutPred

0.22

Gain of stability (P = 0.0417);

MVP

0.77

MPC

0.51

ClinPred

0.73

GERP RS

5.6

Varity_R

0.21

gMVP

0.54

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