dbSNP rs144970008: ZNF41:p.Ala666Val (chrX-47447773-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -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. 12/18 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

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

non-syndromic X-linked intellectual disability
Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

ZNF41 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 368361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 71 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001324144.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF41	NM_001324144.2	MANE Select	c.1997C>T	p.Ala666Val	missense	Exon 5 of 5	NP_001311073.1	P51814-6
ZNF41	NM_001324155.1		c.2123C>T	p.Ala708Val	missense	Exon 4 of 4	NP_001311084.1	P51814-1
ZNF41	NM_001324154.1		c.2099C>T	p.Ala700Val	missense	Exon 4 of 4	NP_001311083.1	P51814-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF41	ENST00000684689.1	MANE Select	c.1997C>T	p.Ala666Val	missense	Exon 5 of 5	ENSP00000508254.1	P51814-6
ZNF41	ENST00000313116.11	TSL:1	c.1997C>T	p.Ala666Val	missense	Exon 5 of 5	ENSP00000315173.7	P51814-6
ZNF41	ENST00000377065.8	TSL:1	c.1997C>T	p.Ala666Val	missense	Exon 5 of 5	ENSP00000366265.4	P51814-6

Frequencies

GnomAD3 genomes

AF:

0.00201

AC:

224

AN:

111660

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00294

AC:

540

AN:

183443

AF XY:

0.00354

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 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

African (AFR)

AF:

0.000341

AC:

AN:

26403

American (AMR)

AF:

0.00148

AC:

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.00454

AC:

AN:

19386

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.00984

AC:

533

AN:

54149

European-Finnish (FIN)

AF:

0.000370

AC:

AN:

40524

Middle Eastern (MID)

AF:

0.00411

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.00340

AC:

2867

AN:

842118

Other (OTH)

AF:

0.00289

AC:

133

AN:

46096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

171

341

512

682

853

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00201

AC:

224

AN:

111714

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

AN XY:

33918

show subpopulations

African (AFR)

AF:

0.000325

AC:

AN:

30814

American (AMR)

AF:

0.00115

AC:

AN:

10434

Ashkenazi Jewish (ASJ)

AF:

0.00454

AC:

AN:

2643

East Asian (EAS)

AF:

0.000282

AC:

AN:

3543

South Asian (SAS)

AF:

0.0101

AC:

AN:

2668

European-Finnish (FIN)

AF:

0.000994

AC:

AN:

6039

Middle Eastern (MID)

AF:

0.00459

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00280

AC:

149

AN:

53153

Other (OTH)

AF:

0.00396

AC:

AN:

1517

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00264

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

History of neurodevelopmental disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Uncertain

1.0

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0051

MetaSVM

Benign

-1.1

PhyloP100

-0.37

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.1

REVEL

Benign

0.066

Sift

Benign

0.049

Sift4G

Benign

0.24

Polyphen

0.078

Vest4

0.058

MVP

0.65

MPC

0.55

ClinPred

0.011

GERP RS

2.8

gMVP

0.11

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over