X-47448023-C-T

Position:

• chrX-47448023-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001324144.2(ZNF41):​c.1747G>A​(p.Asp583Asn) 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. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ZNF41 NM_001324144.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.683

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12805107).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF41	NM_001324144.2	c.1747G>A	p.Asp583Asn	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	c.1747G>A	p.Asp583Asn	missense_variant	5/5		NM_001324144.2	ENSP00000508254.1
ZNF41	ENST00000313116.11	c.1747G>A	p.Asp583Asn	missense_variant	5/5	1		ENSP00000315173.7
ZNF41	ENST00000377065.8	c.1747G>A	p.Asp583Asn	missense_variant	5/5	1		ENSP00000366265.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2024

The c.1747G>A (p.D583N) alteration is located in exon 5 (coding exon 4) of the ZNF41 gene. This alteration results from a G to A substitution at nucleotide position 1747, causing the aspartic acid (D) at amino acid position 583 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	17
DANN	Uncertain	1.0
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.30	.;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.046
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.024	D;D
Polyphen		0.065	B;B
Vest4		0.19
MVP		0.63
MPC		0.26
ClinPred		0.18	T
GERP RS		3.1
gMVP		0.036

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

Other links and lift over

dbSNP: rs1271584158; hg19: chrX-47307422;