X-15815730-G-A

Variant names:

• chrX-15815730-G-A
• rs1932960051
• NM_005089.4:c.611G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005089.4(ZRSR2):​c.611G>A​(p.Ser204Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000089 in 112,356 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
• Consequence: ZRSR2 NM_005089.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.48
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.384305).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005089.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZRSR2	NM_005089.4	MANE Select	c.611G>A	p.Ser204Asn	missense	Exon 8 of 11	NP_005080.1	Q15696

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZRSR2	ENST00000307771.8	TSL:1 MANE Select	c.611G>A	p.Ser204Asn	missense	Exon 8 of 11	ENSP00000303015.7	Q15696
	ZRSR2	ENST00000964213.1		c.629G>A	p.Ser210Asn	missense	Exon 8 of 11	ENSP00000634272.1
	ZRSR2	ENST00000964212.1		c.611G>A	p.Ser204Asn	missense	Exon 8 of 11	ENSP00000634271.1

Frequencies

GnomAD3 genomes AF: 0.00000890 AC: 1 AN: 112356 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000890 AC: 1 AN: 112356 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34516

African (AFR) AF: 0.00 AC: 0 AN: 30899

American (AMR) AF: 0.00 AC: 0 AN: 10610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3614

South Asian (SAS) AF: 0.00 AC: 0 AN: 2747

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6137

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53260

Other (OTH) AF: 0.00 AC: 0 AN: 1516

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.041	T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	0.61	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	-0.96	N
PhyloP100		6.5
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.10	N
REVEL	Uncertain	0.43
Sift	Benign	0.59	T
Sift4G	Benign	1.0	T
Polyphen		0.40	B
Vest4		0.48
MutPred		0.47		Loss of disorder (P = 0.0759)
MVP		0.73
MPC		0.45
ClinPred		0.79	D
GERP RS		5.4
Varity_R		0.32
gMVP		0.74
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1932960051; hg19: chrX-15833853;