Variant X-47448192-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001324144.2(ZNF41):c.1578T>A(p.Ala526=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00315 in 1,210,076 control chromosomes in the GnomAD database, including 9 homozygotes. There are 1,222 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., 99 hem., cov: 22)

Exomes 𝑓: 0.0032 ( 8 hom. 1123 hem. )

Consequence

ZNF41
NM_001324144.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.24

Variant links:

Genes affected

ZNF41 (HGNC:13107): (zinc finger protein 41) This gene encodes a protein that contains KRAB-A and KRAB-B domains multiple zinc finger DNA binding motifs and finger linking regions characteristic of the Kruppel family. An initial study suggested that this gene may be associated with X-linked cognitive disability, but a later study has called this finding into question (PMID:23871722).[provided by RefSeq, Apr 2016]

ZNF41 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant X-47448192-A-T is Benign according to our data. Variant chrX-47448192-A-T is described in ClinVar as [Benign]. Clinvar id is 368363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-47448192-A-T is described in Lovd as [Benign]. Variant chrX-47448192-A-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-4.24 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 99 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF41	NM_001324144.2 linkuse as main transcript	c.1578T>A	p.Ala526=	synonymous_variant	5/5	ENST00000684689.1	NP_001311073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF41	ENST00000684689.1 linkuse as main transcript	c.1578T>A	p.Ala526=	synonymous_variant	5/5		NM_001324144.2	ENSP00000508254	P1	P51814-6
ZNF41	ENST00000313116.11 linkuse as main transcript	c.1578T>A	p.Ala526=	synonymous_variant	5/5	1		ENSP00000315173	P1	P51814-6
ZNF41	ENST00000377065.8 linkuse as main transcript	c.1578T>A	p.Ala526=	synonymous_variant	5/5	1		ENSP00000366265	P1	P51814-6

Frequencies

GnomAD3 genomes

AF:

0.00270

AC:

302

AN:

111812

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

AN XY:

33984

show subpopulations

Gnomad AFR

AF:

0.000358

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.000377

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00795

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00421

Gnomad OTH

AF:

0.00466

GnomAD3 exomes

AF:

0.00246

AC:

452

AN:

183441

Hom.:

AF XY:

0.00236

AC XY:

160

AN XY:

67895

show subpopulations

Gnomad AFR exome

AF:

0.000304

Gnomad AMR exome

AF:

0.00102

Gnomad ASJ exome

AF:

0.000668

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00694

Gnomad NFE exome

AF:

0.00346

Gnomad OTH exome

AF:

0.00464

GnomAD4 exome

AF:

0.00320

AC:

3513

AN:

1098209

Hom.:

Cov.:

AF XY:

0.00309

AC XY:

1123

AN XY:

363567

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.000464

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000923

Gnomad4 FIN exome

AF:

0.00735

Gnomad4 NFE exome

AF:

0.00359

Gnomad4 OTH exome

AF:

0.00282

GnomAD4 genome

AF:

0.00270

AC:

302

AN:

111867

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

AN XY:

34049

show subpopulations

Gnomad4 AFR

AF:

0.000357

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.000377

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00795

Gnomad4 NFE

AF:

0.00421

Gnomad4 OTH

AF:

0.00460

Alfa

AF:

0.00480

Hom.:

Bravo

AF:

0.00181

EpiCase

AF:

0.00256

EpiControl

AF:

0.00273

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 22, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.7

DANN

Benign

0.58

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