Variant X-47456440-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PVS1_ModerateBP6_ModerateBS2

The NM_001324155.1(ZNF41):c.159-2A>C variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000496 in 1,208,674 control chromosomes in the GnomAD database, including 1 homozygotes. There are 172 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., 34 hem., cov: 23)

Exomes 𝑓: 0.00043 ( 1 hom. 138 hem. )

Consequence

ZNF41
NM_001324155.1 splice_acceptor, intron

Scores

Splicing: ADA: 0.00006790

Clinical Significance

Likely benign criteria provided, single submitter U:1B:2

Conservation

PhyloP100: -0.497

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:

ZNF41 (HGNC:):

ZNF41 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.06731549 fraction of the gene. Cryptic splice site detected, with MaxEntScore 5.9, offset of 24, new splice context is: gaccatgctgccttgaacAGcat. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

BP6

Variant X-47456440-T-G is Benign according to our data. Variant chrX-47456440-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 9761.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 34 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF41	NM_001324144.2 linkuse as main transcript	c.73-42A>C		intron_variant		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.73-42A>C		intron_variant			NM_001324144.2	ENSP00000508254.1		P51814-6

Frequencies

GnomAD3 genomes

AF:

0.00112

AC:

125

AN:

112048

Hom.:

Cov.:

AF XY:

0.000993

AC XY:

AN XY:

34224

show subpopulations

Gnomad AFR

AF:

0.00273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000856

Gnomad ASJ

AF:

0.00793

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000131

Gnomad OTH

AF:

0.00265

GnomAD3 exomes

AF:

0.000646

AC:

118

AN:

182638

Hom.:

AF XY:

0.000536

AC XY:

AN XY:

67134

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.000695

Gnomad ASJ exome

AF:

0.00643

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000188

Gnomad NFE exome

AF:

0.000209

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.000433

AC:

475

AN:

1096626

Hom.:

Cov.:

AF XY:

0.000381

AC XY:

138

AN XY:

362016

show subpopulations

Gnomad4 AFR exome

AF:

0.00303

Gnomad4 AMR exome

AF:

0.000796

Gnomad4 ASJ exome

AF:

0.00646

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000248

Gnomad4 NFE exome

AF:

0.000210

Gnomad4 OTH exome

AF:

0.00122

GnomAD4 genome

AF:

0.00112

AC:

125

AN:

112048

Hom.:

Cov.:

AF XY:

0.000993

AC XY:

AN XY:

34224

show subpopulations

Gnomad4 AFR

AF:

0.00273

Gnomad4 AMR

AF:

0.000856

Gnomad4 ASJ

AF:

0.00793

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000131

Gnomad4 OTH

AF:

0.00265

Alfa

AF:

0.000469

Hom.:

Bravo

AF:

0.00129

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00313

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000601

AC:

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2023	ZNF41: BS1 -
Uncertain significance, no assertion criteria provided	literature only	OMIM	Aug 08, 2013	- -

ZNF41-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 13, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.67

FATHMM_MKL

Benign

0.032

GERP RS

-1.6

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000068

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.25

Position offset: -26

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