X-47448121-G-C

Variant names:

• chrX-47448121-G-C
• NM_001324144.2:c.1649C>G

Variant summary

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

The NM_001324144.2(ZNF41):​c.1649C>G​(p.Pro550Arg) variant causes a missense change. 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: 3.98

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.1649C>G	p.Pro550Arg	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.1649C>G	p.Pro550Arg	missense_variant	Exon 5 of 5		NM_001324144.2	ENSP00000508254.1
ZNF41	ENST00000313116.11	c.1649C>G	p.Pro550Arg	missense_variant	Exon 5 of 5	1		ENSP00000315173.7
ZNF41	ENST00000377065.8	c.1649C>G	p.Pro550Arg	missense_variant	Exon 5 of 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 provided Uncertain:1

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ZNF41: PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	23
DANN	Uncertain	1.0
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.077	.;T
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Benign	-0.91	T
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-8.1	D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;D
Vest4		0.44
MVP		0.73
MPC		0.91
ClinPred		1.0	D
GERP RS		4.0
gMVP		0.10

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-47307520;