X-47447950-T-A

Variant names:

• chrX-47447950-T-A
• NM_001324144.2:c.1820A>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.1820A>T​(p.Tyr607Phe) 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. 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: -1.53

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=0.09835124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF41	NM_001324144.2	c.1820A>T	p.Tyr607Phe	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.1820A>T	p.Tyr607Phe	missense_variant	Exon 5 of 5		NM_001324144.2	ENSP00000508254.1
ZNF41	ENST00000313116.11	c.1820A>T	p.Tyr607Phe	missense_variant	Exon 5 of 5	1		ENSP00000315173.7
ZNF41	ENST00000377065.8	c.1820A>T	p.Tyr607Phe	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 specified Uncertain:1

Mar 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1820A>T (p.Y607F) alteration is located in exon 5 (coding exon 4) of the ZNF41 gene. This alteration results from a A to T substitution at nucleotide position 1820, causing the tyrosine (Y) at amino acid position 607 to be replaced by a phenylalanine (F). 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	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	18
DANN	Uncertain	0.98
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.43	.;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.098	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.036
Sift	Uncertain	0.0010	D;D
Sift4G	Benign	0.081	T;T
Polyphen		0.0030	B;B
Vest4		0.28
MVP		0.63
MPC		0.78
ClinPred		0.23	T
GERP RS		2.8
gMVP		0.056

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-47307349;