chrX-153347101-G-A

Position:

• chrX-153347101-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001367757.1(ZNF275):​c.416G>A​(p.Arg139Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,097,763 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.000020 (0 hom. 2 hem.)
• Consequence: ZNF275 NM_001367757.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.033518046).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF275	NM_001367757.1	c.416G>A	p.Arg139Lys	missense_variant	4/4	ENST00000650114.2
ZNF275	NM_001080485.4	c.416G>A	p.Arg139Lys	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF275	ENST00000650114.2	c.416G>A	p.Arg139Lys	missense_variant	4/4		NM_001367757.1	A2
ZNF275	ENST00000370249.3	c.257G>A	p.Arg86Lys	missense_variant	3/3	1		P2
ZNF275	ENST00000370251.3	c.416G>A	p.Arg139Lys	missense_variant	4/5	2
ZNF275	ENST00000647705.1	n.1628G>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.000117 AC: 21 AN: 180208 Hom.: 0 AF XY: 0.0000301 AC XY: 2 AN XY: 66338

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000770

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000200 AC: 22 AN: 1097763 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 2 AN XY: 363199

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000625

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

Bravo AF: 0.0000264

ExAC AF: 0.0000413 AC: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.1
DANN	Uncertain	0.98
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.37	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.034	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.2	N;.;N
REVEL	Benign	0.018
Sift	Benign	0.27	T;.;T
Sift4G	Benign	0.32	T;.;T
Polyphen		0.55	.;P;P
Vest4		0.051
MutPred		0.38		.;Gain of methylation at R139 (P = 0.0039);Gain of methylation at R139 (P = 0.0039);
MVP		0.32
MPC		0.35
ClinPred		0.063	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.086
gMVP		0.26

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: rs781852052; hg19: chrX-152612559;