rs142064485

Variant names:

• chrX-15820309-G-A
• rs142064485
• NM_005089.4:c.930G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-15820309-G-A
• chrX-15820309-G-C
• chrX-15820309-G-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_005089.4(ZRSR2):​c.930G>A​(p.Ala310Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000724 in 1,205,247 control chromosomes in the GnomAD database, including 8 homozygotes. There are 241 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A310A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0039 (5 hom., 122 hem., cov: 23)
  • Exomes 𝑓: 0.00040 (3 hom. 119 hem.)
• Consequence: ZRSR2 NM_005089.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.718
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-0.718 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZRSR2	NM_005089.4	c.930G>A	p.Ala310Ala	synonymous_variant	Exon 10 of 11	ENST00000307771.8	NP_005080.1
ZRSR2	XM_011545589.4	c.999G>A	p.Ala333Ala	synonymous_variant	Exon 9 of 10		XP_011543891.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZRSR2	ENST00000307771.8	c.930G>A	p.Ala310Ala	synonymous_variant	Exon 10 of 11	1	NM_005089.4	ENSP00000303015.7
ZRSR2	ENST00000684799.1	c.852G>A	p.Ala284Ala	synonymous_variant	Exon 9 of 11			ENSP00000510773.1
ZRSR2	ENST00000690252.1	n.930G>A		non_coding_transcript_exon_variant	Exon 10 of 13			ENSP00000510140.1
ZRSR2	ENST00000691502.1	n.930G>A		non_coding_transcript_exon_variant	Exon 10 of 13			ENSP00000509336.1

Frequencies

GnomAD3 genomes AF: 0.00390 AC: 437 AN: 112058 Hom.: 5 Cov.: 23

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00114

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: 0.00397

GnomAD2 exomes AF: 0.00119 AC: 218 AN: 182552 AF XY: 0.000716

Gnomad AFR exome AF: 0.0156

Gnomad AMR exome AF: 0.000257

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000368

Gnomad OTH exome AF: 0.000445

GnomAD4 exome AF: 0.000397 AC: 434 AN: 1093136 Hom.: 3 Cov.: 29 AF XY: 0.000332 AC XY: 119 AN XY: 358600

African (AFR) AF: 0.0134 AC: 353 AN: 26319

American (AMR) AF: 0.000569 AC: 20 AN: 35162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19351

East Asian (EAS) AF: 0.00 AC: 0 AN: 30157

South Asian (SAS) AF: 0.0000556 AC: 3 AN: 53971

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40512

Middle Eastern (MID) AF: 0.000727 AC: 3 AN: 4125

European-Non Finnish (NFE) AF: 0.0000131 AC: 11 AN: 837605

Other (OTH) AF: 0.000958 AC: 44 AN: 45934

GnomAD4 genome AF: 0.00391 AC: 438 AN: 112111 Hom.: 5 Cov.: 23 AF XY: 0.00356 AC XY: 122 AN XY: 34283

African (AFR) AF: 0.0135 AC: 418 AN: 30887

American (AMR) AF: 0.00114 AC: 12 AN: 10561

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3579

South Asian (SAS) AF: 0.000370 AC: 1 AN: 2701

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6061

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53233

Other (OTH) AF: 0.00392 AC: 6 AN: 1531

Alfa AF: 0.00169 Hom.: 7

Bravo AF: 0.00440

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.1
DANN	Benign	0.80
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs142064485; hg19: chrX-15838432;