X-47447656-C-T

Position:

chrX-47447656-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001324144.2(ZNF41):c.2114G>A(p.Arg705His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000379 in 1,209,810 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 158 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., 13 hem., cov: 23)

Exomes 𝑓: 0.00037 ( 0 hom. 145 hem. )

Consequence

ZNF41
NM_001324144.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: -1.82

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028129935).

BP6

Variant X-47447656-C-T is Benign according to our data. Variant chrX-47447656-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 368360.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}. Variant chrX-47447656-C-T is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 13 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF41	NM_001324144.2 linkuse as main transcript	c.2114G>A	p.Arg705His	missense_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.2114G>A	p.Arg705His	missense_variant	5/5		NM_001324144.2	ENSP00000508254	P1	P51814-6
ZNF41	ENST00000313116.11 linkuse as main transcript	c.2114G>A	p.Arg705His	missense_variant	5/5	1		ENSP00000315173	P1	P51814-6
ZNF41	ENST00000377065.8 linkuse as main transcript	c.2114G>A	p.Arg705His	missense_variant	5/5	1		ENSP00000366265	P1	P51814-6

Frequencies

GnomAD3 genomes

AF:

0.000457

AC:

AN:

111640

Hom.:

Cov.:

AF XY:

0.000384

AC XY:

AN XY:

33836

show subpopulations

Gnomad AFR

AF:

0.000488

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000960

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000664

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000583

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000360

AC:

AN:

183193

Hom.:

AF XY:

0.000384

AC XY:

AN XY:

67691

show subpopulations

Gnomad AFR exome

AF:

0.000760

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.000439

Gnomad NFE exome

AF:

0.000514

Gnomad OTH exome

AF:

0.000442

GnomAD4 exome

AF:

0.000371

AC:

407

AN:

1098170

Hom.:

Cov.:

AF XY:

0.000399

AC XY:

145

AN XY:

363532

show subpopulations

Gnomad4 AFR exome

AF:

0.000189

Gnomad4 AMR exome

AF:

0.000227

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00101

Gnomad4 NFE exome

AF:

0.000395

Gnomad4 OTH exome

AF:

0.000347

GnomAD4 genome

AF:

0.000457

AC:

AN:

111640

Hom.:

Cov.:

AF XY:

0.000384

AC XY:

AN XY:

33836

show subpopulations

Gnomad4 AFR

AF:

0.000488

Gnomad4 AMR

AF:

0.0000960

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000664

Gnomad4 NFE

AF:

0.000583

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000852

Hom.:

Bravo

AF:

0.000457

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.000595

AC:

ExAC

AF:

0.000404

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.000415

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	ZNF41: BS2 -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

History of neurodevelopmental disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2011

There is insufficient or conflicting evidence for classification of this alteration. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Uncertain

1.0

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.16

.;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-0.90

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.20

N;N

REVEL

Benign

0.062

Sift

Benign

0.65

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.22

B;B

Vest4

0.048

MVP

0.64

MPC

0.30

ClinPred

0.015

GERP RS

3.7

gMVP

0.13

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