NM_001324144.2:c.2004T>C

Variant names:

• chrX-47447766-A-G
• rs373412941
• NM_001324144.2:c.2004T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001324144.2(ZNF41):​c.2004T>C​(p.Cys668Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,209,961 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 93 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000063 (0 hom., 2 hem., cov: 22)
  • Exomes 𝑓: 0.00022 (0 hom. 91 hem.)
• Consequence: ZNF41 NM_001324144.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.16
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant X-47447766-A-G is Benign according to our data. Variant chrX-47447766-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1784303.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.16 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 2 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF41	NM_001324144.2	MANE Select	c.2004T>C	p.Cys668Cys	synonymous	Exon 5 of 5	NP_001311073.1	P51814-6
	ZNF41	NM_001324155.1		c.2130T>C	p.Cys710Cys	synonymous	Exon 4 of 4	NP_001311084.1	P51814-1
	ZNF41	NM_001324154.1		c.2106T>C	p.Cys702Cys	synonymous	Exon 4 of 4	NP_001311083.1	P51814-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF41	ENST00000684689.1	MANE Select	c.2004T>C	p.Cys668Cys	synonymous	Exon 5 of 5	ENSP00000508254.1	P51814-6
	ZNF41	ENST00000313116.11	TSL:1	c.2004T>C	p.Cys668Cys	synonymous	Exon 5 of 5	ENSP00000315173.7	P51814-6
	ZNF41	ENST00000377065.8	TSL:1	c.2004T>C	p.Cys668Cys	synonymous	Exon 5 of 5	ENSP00000366265.4	P51814-6

Frequencies

GnomAD3 genomes AF: 0.0000626 AC: 7 AN: 111739 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000113

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000709 AC: 13 AN: 183440 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000147

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.000218 AC: 239 AN: 1098222 Hom.: 0 Cov.: 32 AF XY: 0.000250 AC XY: 91 AN XY: 363590

African (AFR) AF: 0.0000379 AC: 1 AN: 26403

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4133

European-Non Finnish (NFE) AF: 0.000270 AC: 227 AN: 842117

Other (OTH) AF: 0.000239 AC: 11 AN: 46096

GnomAD4 genome AF: 0.0000626 AC: 7 AN: 111739 Hom.: 0 Cov.: 22 AF XY: 0.0000590 AC XY: 2 AN XY: 33909

African (AFR) AF: 0.0000325 AC: 1 AN: 30773

American (AMR) AF: 0.00 AC: 0 AN: 10454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3553

South Asian (SAS) AF: 0.00 AC: 0 AN: 2673

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.000113 AC: 6 AN: 53173

Other (OTH) AF: 0.00 AC: 0 AN: 1500

Alfa AF: 0.000285 Hom.: 2

Bravo AF: 0.0000793

EpiCase AF: 0.000109

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.3
DANN	Benign	0.52
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs373412941; hg19: chrX-47307165;