chrX-153347766-C-T

Position:

• chrX-153347766-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001367757.1(ZNF275):​c.1081C>T​(p.Pro361Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,093,474 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.000014 (0 hom. 4 hem.)
• Consequence: ZNF275 NM_001367757.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.592

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_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07369396).
• BS2: High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF275	NM_001367757.1	c.1081C>T	p.Pro361Ser	missense_variant	4/4	ENST00000650114.2	NP_001354686.1
ZNF275	NM_001080485.4	c.983C>T	p.Ala328Val	missense_variant	5/5		NP_001073954.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF275	ENST00000650114.2	c.1081C>T	p.Pro361Ser	missense_variant	4/4		NM_001367757.1	ENSP00000496975	A2
ZNF275	ENST00000370249.3	c.922C>T	p.Pro308Ser	missense_variant	3/3	1		ENSP00000359269	P2
ZNF275	ENST00000370251.3	c.983C>T	p.Ala328Val	missense_variant	5/5	2		ENSP00000359271
ZNF275	ENST00000647705.1	n.2293C>T		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 0.0000137 AC: 15 AN: 1093474 Hom.: 0 Cov.: 33 AF XY: 0.0000111 AC XY: 4 AN XY: 359536

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000167

Gnomad4 OTH exome AF: 0.0000218

GnomAD4 genome Cov.: 26

Bravo AF: 0.00000378

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 01, 2024

The c.983C>T (p.A328V) alteration is located in exon 5 (coding exon 4) of the ZNF275 gene. This alteration results from a C to T substitution at nucleotide position 983, causing the alanine (A) at amino acid position 328 to be replaced by a valine (V). 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	0.58
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	17
DANN	Benign	0.88
DEOGEN2	Benign	0.029	T
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.033
Sift	Pathogenic	0.0	D
Polyphen		0.0070	B
Vest4		0.089
MVP		0.34
MPC		0.34
ClinPred		0.089	T
GERP RS		3.4
gMVP		0.46

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

LitVar

Other links and lift over

dbSNP: rs2088529608; hg19: chrX-152613224;