Variant X-47447773-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.1997C>T(p.Ala666Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00325 in 1,209,939 control chromosomes in the GnomAD database, including 11 homozygotes. There are 1,348 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., 71 hem., cov: 22)

Exomes 𝑓: 0.0034 ( 11 hom. 1277 hem. )

Consequence

ZNF41
NM_001324144.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.373

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=0.005091071).

BP6

Variant X-47447773-G-A is Benign according to our data. Variant chrX-47447773-G-A is described in ClinVar as [Benign]. Clinvar id is 368361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-47447773-G-A is described in Lovd as [Benign]. Variant chrX-47447773-G-A is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 71 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF41	NM_001324144.2 linkuse as main transcript	c.1997C>T	p.Ala666Val	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.1997C>T	p.Ala666Val	missense_variant	5/5		NM_001324144.2	ENSP00000508254	P1	P51814-6
ZNF41	ENST00000313116.11 linkuse as main transcript	c.1997C>T	p.Ala666Val	missense_variant	5/5	1		ENSP00000315173	P1	P51814-6
ZNF41	ENST00000377065.8 linkuse as main transcript	c.1997C>T	p.Ala666Val	missense_variant	5/5	1		ENSP00000366265	P1	P51814-6

Frequencies

GnomAD3 genomes

AF:

0.00201

AC:

224

AN:

111660

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

AN XY:

33854

show subpopulations

Gnomad AFR

AF:

0.000325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00115

Gnomad ASJ

AF:

0.00454

Gnomad EAS

AF:

0.000281

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.000994

Gnomad MID

AF:

0.00420

Gnomad NFE

AF:

0.00280

Gnomad OTH

AF:

0.00401

GnomAD3 exomes

AF:

0.00294

AC:

540

AN:

183443

Hom.:

AF XY:

0.00354

AC XY:

240

AN XY:

67889

show subpopulations

Gnomad AFR exome

AF:

0.000304

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.00588

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0115

Gnomad FIN exome

AF:

0.000313

Gnomad NFE exome

AF:

0.00267

Gnomad OTH exome

AF:

0.00287

GnomAD4 exome

AF:

0.00338

AC:

3714

AN:

1098225

Hom.:

Cov.:

AF XY:

0.00351

AC XY:

1277

AN XY:

363581

show subpopulations

Gnomad4 AFR exome

AF:

0.000341

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.00454

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00984

Gnomad4 FIN exome

AF:

0.000370

Gnomad4 NFE exome

AF:

0.00340

Gnomad4 OTH exome

AF:

0.00289

GnomAD4 genome

AF:

0.00201

AC:

224

AN:

111714

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

AN XY:

33918

show subpopulations

Gnomad4 AFR

AF:

0.000325

Gnomad4 AMR

AF:

0.00115

Gnomad4 ASJ

AF:

0.00454

Gnomad4 EAS

AF:

0.000282

Gnomad4 SAS

AF:

0.0101

Gnomad4 FIN

AF:

0.000994

Gnomad4 NFE

AF:

0.00280

Gnomad4 OTH

AF:

0.00396

Alfa

AF:

0.00299

Hom.:

149

Bravo

AF:

0.00181

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00223

AC:

ExAC

AF:

0.00297

AC:

361

EpiCase

AF:

0.00338

EpiControl

AF:

0.00243

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

History of neurodevelopmental disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 28, 2016

General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Uncertain

1.0

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.24

.;T

MetaRNN

Benign

0.0051

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.066

Sift

Benign

0.049

D;D

Sift4G

Benign

0.24

T;T

Polyphen

0.078

B;B

Vest4

0.058

MVP

0.65

MPC

0.55

ClinPred

0.011

GERP RS

2.8

gMVP

0.11

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