X-47410361-A-G

Position:

• chrX-47410361-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000377073.4(ZNF157):​c.158A>G​(p.Lys53Arg) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ZNF157 ENST00000377073.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0750

Genes affected

ZNF157 (HGNC:12942): (zinc finger protein 157) This gene product is a likely zinc finger family transcription factor. It contains KRAB-A and KRAB-B domains that act as transcriptional repressors in related proteins, and multiple zinc finger DNA binding motifs and finger linking regions characteristic of the Kruppel family. This gene is part of a gene cluster on chromosome Xp11.23. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03592834).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF157	NM_003446.4	c.158A>G	p.Lys53Arg	missense_variant	2/4	ENST00000377073.4	NP_003437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF157	ENST00000377073.4	c.158A>G	p.Lys53Arg	missense_variant	2/4	1	NM_003446.4	ENSP00000366273.4

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

Apr 24, 2024

The c.158A>G (p.K53R) alteration is located in exon 2 (coding exon 2) of the ZNF157 gene. This alteration results from a A to G substitution at nucleotide position 158, causing the lysine (K) at amino acid position 53 to be replaced by an arginine (R). 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
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.96
CADD	Benign	17
DANN	Benign	0.28
DEOGEN2	Benign	0.0032	T
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.9	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.030
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0060	B
Vest4		0.096
MutPred		0.60		Loss of methylation at K53 (P = 0.0144);
MVP		0.30
MPC		0.024
ClinPred		0.043	T
GERP RS		0.32
Varity_R		0.089
gMVP		0.45

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-47269760;