X-47448023-C-G

Variant names:

• chrX-47448023-C-G
• rs1271584158
• NM_001324144.2:c.1747G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001324144.2(ZNF41):​c.1747G>C​(p.Asp583His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D583N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: ZNF41 NM_001324144.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10370502).

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.1747G>C	p.Asp583His	missense	Exon 5 of 5	NP_001311073.1	P51814-6
	ZNF41	NM_001324155.1		c.1873G>C	p.Asp625His	missense	Exon 4 of 4	NP_001311084.1	P51814-1
	ZNF41	NM_001324154.1		c.1849G>C	p.Asp617His	missense	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.1747G>C	p.Asp583His	missense	Exon 5 of 5	ENSP00000508254.1	P51814-6
	ZNF41	ENST00000313116.11	TSL:1	c.1747G>C	p.Asp583His	missense	Exon 5 of 5	ENSP00000315173.7	P51814-6
	ZNF41	ENST00000377065.8	TSL:1	c.1747G>C	p.Asp583His	missense	Exon 5 of 5	ENSP00000366265.4	P51814-6

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 111132 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 111132 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33468

African (AFR) AF: 0.00 AC: 0 AN: 30516

American (AMR) AF: 0.00 AC: 0 AN: 10402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2630

East Asian (EAS) AF: 0.00 AC: 0 AN: 3538

South Asian (SAS) AF: 0.00 AC: 0 AN: 2667

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 233

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52963

Other (OTH) AF: 0.00 AC: 0 AN: 1496

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	17
DANN	Uncertain	0.99
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.68
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.028
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.10	T
Polyphen		0.0070	B
Vest4		0.20
MVP		0.33
MPC		0.46
ClinPred		0.35	T
GERP RS		3.1
gMVP		0.13
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: rs1271584158; hg19: chrX-47307422;