rs188867560

chrX-15803767-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_005089.4(ZRSR2):c.283G>A(p.Ala95Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000529 in 1,193,897 control chromosomes in the GnomAD database, including 4 homozygotes. There are 178 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.00051 (1 hom., 16 hem., cov: 22)
  • Exomes 𝑓: 0.00053 (3 hom. 162 hem.)
• Consequence: ZRSR2 NM_005089.4 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 4.67

Genes affected

ZRSR2 (HGNC:23019): (zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2) This gene encodes an essential splicing factor. The encoded protein associates with the U2 auxiliary factor heterodimer, which is required for the recognition of a functional 3' splice site in pre-mRNA splicing, and may play a role in network interactions during spliceosome assembly. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0044573843).
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000531 (575/1083604) while in subpopulation EAS AF= 0.0166 (491/29652). AF 95% confidence interval is 0.0153. There are 3 homozygotes in gnomad4_exome. There are 162 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Hemizygotes in GnomAd at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZRSR2	NM_005089.4	c.283G>A	p.Ala95Thr	missense_variant	4/11	ENST00000307771.8
ZRSR2	XM_011545589.4	c.352G>A	p.Ala118Thr	missense_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZRSR2	ENST00000307771.8	c.283G>A	p.Ala95Thr	missense_variant	4/11	1	NM_005089.4	P2

Frequencies

GnomAD3 genomes AF: 0.000517 AC: 57 AN: 110239 Hom.: 1 Cov.: 22 AF XY: 0.000524 AC XY: 17 AN XY: 32461

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000983

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0158

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00162 AC: 254 AN: 156370 Hom.: 2 AF XY: 0.00133 AC XY: 65 AN XY: 48738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000400

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0202

Gnomad SAS exome AF: 0.000311

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000977

GnomAD4 exome AF: 0.000531 AC: 575 AN: 1083604 Hom.: 3 Cov.: 30 AF XY: 0.000459 AC XY: 162 AN XY: 353122

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000298

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0166

Gnomad4 SAS exome AF: 0.000404

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00129

GnomAD4 genome AF: 0.000508 AC: 56 AN: 110293 Hom.: 1 Cov.: 22 AF XY: 0.000492 AC XY: 16 AN XY: 32525

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000982

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0156

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000789 Hom.: 15

Bravo AF: 0.000631

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.00151 AC: 182

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.21
Cadd	Benign	20
Dann	Uncertain	0.99
DEOGEN2	Benign	0.039	T
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.0045	T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.34
Sift	Benign	0.20	T
Sift4G	Benign	0.26	T
Polyphen		0.20	B
Vest4		0.12
MVP		0.72
MPC		0.39
ClinPred		0.023	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.13

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: rs188867560; hg19: chrX-15821890;