chrX-153346993-G-T

Position:

• chrX-153346993-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001367757.1(ZNF275):​c.308G>T​(p.Cys103Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ZNF275 NM_001367757.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.86

Genes affected

ZNF275 (HGNC:13069): (zinc finger protein 275) This gene encodes a zinc finger protein that appears to be conserved in eutheria. Its function has not yet been established. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.951

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF275	NM_001367757.1	c.308G>T	p.Cys103Phe	missense_variant	4/4	ENST00000650114.2
ZNF275	NM_001080485.4	c.308G>T	p.Cys103Phe	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF275	ENST00000650114.2	c.308G>T	p.Cys103Phe	missense_variant	4/4		NM_001367757.1	A2
ZNF275	ENST00000370249.3	c.149G>T	p.Cys50Phe	missense_variant	3/3	1		P2
ZNF275	ENST00000370251.3	c.308G>T	p.Cys103Phe	missense_variant	4/5	2
ZNF275	ENST00000647705.1	n.1520G>T		non_coding_transcript_exon_variant	2/2

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

Nov 18, 2022

The c.308G>T (p.C103F) alteration is located in exon 4 (coding exon 3) of the ZNF275 gene. This alteration results from a G to T substitution at nucleotide position 308, causing the cysteine (C) at amino acid position 103 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
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	27
DANN	Uncertain	0.99
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.058	D
MetaRNN	Pathogenic	0.95	D;D;D
MetaSVM	Uncertain	-0.13	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-9.5	D;.;D
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	D;.;D
Sift4G	Uncertain	0.012	D;.;D
Polyphen		1.0	.;D;D
Vest4		0.74
MutPred		0.80		.;Gain of ubiquitination at K104 (P = 0.0725);Gain of ubiquitination at K104 (P = 0.0725);
MVP		0.91
MPC		1.4
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.97
gMVP		0.58

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-152612451;