X-47447461-C-T

Variant names:

• chrX-47447461-C-T
• NM_001324144.2:c.2309G>A

Variant summary

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

The NM_001324144.2(ZNF41):​c.2309G>A​(p.Ser770Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,889 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: ZNF41 NM_001324144.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310

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=0.07697472).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF41	NM_001324144.2	c.2309G>A	p.Ser770Asn	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.2309G>A	p.Ser770Asn	missense_variant	Exon 5 of 5		NM_001324144.2	ENSP00000508254.1
ZNF41	ENST00000313116.11	c.2309G>A	p.Ser770Asn	missense_variant	Exon 5 of 5	1		ENSP00000315173.7
ZNF41	ENST00000377065.8	c.2309G>A	p.Ser770Asn	missense_variant	Exon 5 of 5	1		ENSP00000366265.4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097889 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363329

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	16
DANN	Uncertain	0.99
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.11	.;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.077	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.71	N;N
REVEL	Benign	0.040
Sift	Benign	0.045	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.0010	B;B
Vest4		0.055
MVP		0.62
MPC		0.23
ClinPred		0.31	T
GERP RS		1.7
gMVP		0.022

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-47306860;