Variant 8-143250426-C-T 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_173832.6(ZFP41):c.583C>T(p.Arg195Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,610,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ZFP41
NM_173832.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.103

Variant links:

Genes affected

ZFP41 (HGNC:26786): (ZFP41 zinc finger protein) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZFP41 links:

ENSG00000264668 (HGNC:):

ENSG00000264668 links:

Genome browser will be placed here

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=0.07032615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP41	NM_173832.6 linkuse as main transcript	c.583C>T	p.Arg195Trp	missense_variant	2/3	ENST00000330701.7	NP_776193.3	Q8N8Y5A0A0G2JH32
ZFP41	NM_001271156.3 linkuse as main transcript	c.583C>T	p.Arg195Trp	missense_variant	2/3		NP_001258085.3	Q8N8Y5A0A0G2JH32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZFP41	ENST00000330701.7 linkuse as main transcript	c.583C>T	p.Arg195Trp	missense_variant	2/3	2	NM_173832.6	ENSP00000327427.6	Q8N8Y5
ZFP41	ENST00000520584.6 linkuse as main transcript	c.583C>T	p.Arg195Trp	missense_variant	2/3	1		ENSP00000430465.3	Q8N8Y5
ENSG00000264668	ENST00000522452.2 linkuse as main transcript	c.583C>T	p.Arg195Trp	missense_variant	2/4	1		ENSP00000428966.3	A0A0G2JH32

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000282

AC:

AN:

247842

Hom.:

AF XY:

0.0000371

AC XY:

AN XY:

134776

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1458284

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

725014

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000262

AC:

AN:

152382

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Jul 14, 2022

The c.583C>T (p.R195W) alteration is located in exon 2 (coding exon 1) of the ZFP41 gene. This alteration results from a C to T substitution at nucleotide position 583, causing the arginine (R) at amino acid position 195 to be replaced by a tryptophan (W). 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

0.29

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.40

.;T;.

M_CAP

Benign

0.013

MetaRNN

Benign

0.070

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.33

REVEL

Benign

0.056

Sift4G

Uncertain

0.0040

D;D;D

Vest4

0.16

MVP

0.25

MPC

0.066

ClinPred

0.26

GERP RS

0.71

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