X-47447463-A-C

Variant names:

• chrX-47447463-A-C
• rs879250867
• NM_001324144.2:c.2307T>G

Variant summary

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

The NM_001324144.2(ZNF41):​c.2307T>G​(p.His769Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: ZNF41 NM_001324144.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690

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 rank	MANE	Protein	UniProt
ZNF41	NM_001324144.2	c.2307T>G	p.His769Gln	missense_variant	Exon 5 of 5	ENST00000684689.1	NP_001311073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF41	ENST00000684689.1	c.2307T>G	p.His769Gln	missense_variant	Exon 5 of 5		NM_001324144.2	ENSP00000508254.1
ZNF41	ENST00000313116.11	c.2307T>G	p.His769Gln	missense_variant	Exon 5 of 5	1		ENSP00000315173.7
ZNF41	ENST00000377065.8	c.2307T>G	p.His769Gln	missense_variant	Exon 5 of 5	1		ENSP00000366265.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Uncertain	0.99
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.52	.;T
M_CAP	Benign	0.0041	T
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-0.71	T
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;D
Vest4		0.59
MVP		0.66
MPC		0.88
ClinPred		1.0	D
GERP RS		-4.2
gMVP		0.047

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: rs879250867; hg19: chrX-47306862;