X-47447586-G-C

Position:

• chrX-47447586-G-C

Variant summary

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

The NM_001324144.2(ZNF41):​c.2184C>G​(p.Phe728Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: -0.0510

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF41	NM_001324144.2	c.2184C>G	p.Phe728Leu	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.2184C>G	p.Phe728Leu	missense_variant	5/5		NM_001324144.2	ENSP00000508254.1
ZNF41	ENST00000313116.11	c.2184C>G	p.Phe728Leu	missense_variant	5/5	1		ENSP00000315173.7
ZNF41	ENST00000377065.8	c.2184C>G	p.Phe728Leu	missense_variant	5/5	1		ENSP00000366265.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

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

Oct 20, 2024

The c.2184C>G (p.F728L) alteration is located in exon 5 (coding exon 4) of the ZNF41 gene. This alteration results from a C to G substitution at nucleotide position 2184, causing the phenylalanine (F) at amino acid position 728 to be replaced by a leucine (L). 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	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Uncertain	1.0
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.68	.;T
M_CAP	Benign	0.0045	T
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.82	T
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0020	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.99	D;D
Vest4		0.65
MVP		0.82
MPC		0.94
ClinPred		0.97	D
GERP RS		-0.98
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-47306985;