rs587778766

chrX-15823100-G-AchrX-15823100-G-C

Variant summary

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

The NM_005089.4(ZRSR2):c.1307G>A(p.Gly436Asp) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ZRSR2 NM_005089.4 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 1.25

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 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=0.048667222).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZRSR2	NM_005089.4	c.1307G>A	p.Gly436Asp	missense_variant	11/11	ENST00000307771.8
ZRSR2	XM_011545589.4	c.1376G>A	p.Gly459Asp	missense_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZRSR2	ENST00000307771.8	c.1307G>A	p.Gly436Asp	missense_variant	11/11	1	NM_005089.4	P2
ZRSR2	ENST00000684799.1	c.1229G>A	p.Gly410Asp	missense_variant	10/11			A2
ZRSR2	ENST00000690252.1	c.1307G>A	p.Gly436Asp	missense_variant, NMD_transcript_variant	11/13
ZRSR2	ENST00000691502.1	c.1193G>A	p.Gly398Asp	missense_variant, NMD_transcript_variant	11/13

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1093283 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 359777

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.9
Dann	Benign	0.90
DEOGEN2	Benign	0.014	T
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.012
Sift	Benign	0.22	T
Sift4G	Benign	0.55	T
Polyphen		0.11	B
Vest4		0.13
MVP		0.14
MPC		0.53
ClinPred		0.065	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.056
gMVP		0.23

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: rs587778766; hg19: chrX-15841223;