X-15815867-G-C

Variant names:

• chrX-15815867-G-C
• NM_005089.4:c.748G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005089.4(ZRSR2):​c.748G>C​(p.Val250Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000914 in 1,094,556 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: ZRSR2 NM_005089.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.54

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3147387).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZRSR2	NM_005089.4	c.748G>C	p.Val250Leu	missense_variant	Exon 8 of 11	ENST00000307771.8	NP_005080.1
ZRSR2	XM_011545589.4	c.817G>C	p.Val273Leu	missense_variant	Exon 7 of 10		XP_011543891.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZRSR2	ENST00000307771.8	c.748G>C	p.Val250Leu	missense_variant	Exon 8 of 11	1	NM_005089.4	ENSP00000303015.7
ZRSR2	ENST00000684799.1	c.670G>C	p.Val224Leu	missense_variant	Exon 7 of 11			ENSP00000510773.1
ZRSR2	ENST00000690252.1	n.748G>C		non_coding_transcript_exon_variant	Exon 8 of 13			ENSP00000510140.1
ZRSR2	ENST00000691502.1	n.748G>C		non_coding_transcript_exon_variant	Exon 8 of 13			ENSP00000509336.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.14e-7 AC: 1 AN: 1094556 Hom.: 0 Cov.: 30 AF XY: 0.00000278 AC XY: 1 AN XY: 360150

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000332

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.54	N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.12
Sift	Benign	0.28	T
Sift4G	Benign	0.54	T
Polyphen		0.60	P
Vest4		0.41
MutPred		0.58		Loss of methylation at K252 (P = 0.0891);
MVP		0.38
MPC		0.75
ClinPred		0.87	D
GERP RS		5.4
Varity_R		0.46
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-15833990;