Variant chrX-47449438-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001324144.2(ZNF41):c.332C>T(p.Pro111Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,207,428 control chromosomes in the GnomAD database, including 1 homozygotes. There are 539 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00063 ( 0 hom., 22 hem., cov: 22)

Exomes 𝑓: 0.0016 ( 1 hom. 517 hem. )

Consequence

ZNF41
NM_001324144.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts U:1B:2

Conservation

PhyloP100: 1.48

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019093096).

BP6

Variant X-47449438-G-A is Benign according to our data. Variant chrX-47449438-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 9760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-47449438-G-A is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 22 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF41	NM_001324144.2 linkuse as main transcript	c.332C>T	p.Pro111Leu	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.332C>T	p.Pro111Leu	missense_variant	5/5		NM_001324144.2	ENSP00000508254	P1	P51814-6

Frequencies

GnomAD3 genomes

AF:

0.000631

AC:

AN:

110869

Hom.:

Cov.:

AF XY:

0.000664

AC XY:

AN XY:

33123

show subpopulations

Gnomad AFR

AF:

0.0000656

Gnomad AMI

AF:

0.00291

Gnomad AMR

AF:

0.000292

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:

0.00117

Gnomad OTH

AF:

0.000672

GnomAD3 exomes

AF:

0.000519

AC:

AN:

179121

Hom.:

AF XY:

0.000515

AC XY:

AN XY:

64021

show subpopulations

Gnomad AFR exome

AF:

0.0000776

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00116

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00160

AC:

1750

AN:

1096559

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

517

AN XY:

361955

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00202

Gnomad4 OTH exome

AF:

0.00104

GnomAD4 genome

AF:

0.000631

AC:

AN:

110869

Hom.:

Cov.:

AF XY:

0.000664

AC XY:

AN XY:

33123

show subpopulations

Gnomad4 AFR

AF:

0.0000656

Gnomad4 AMR

AF:

0.000292

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00117

Gnomad4 OTH

AF:

0.000672

Alfa

AF:

0.00145

Hom.:

Bravo

AF:

0.000714

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00381

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00149

AC:

ExAC

AF:

0.000404

AC:

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Sep 15, 2017	- -
Uncertain significance, no assertion criteria provided	literature only	OMIM	Aug 08, 2013	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	ZNF41: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.56

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.51

.;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.019

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.82

A;A;A

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.98

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.34

T;T;T

Sift4G

Benign

0.44

T;T;.

Polyphen

0.065

B;B;.

Vest4

0.65

MVP

0.26

MPC

0.25

ClinPred

0.022

GERP RS

3.1

gMVP

0.37

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