chrX-15815730-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005089.4(ZRSR2):​c.611G>T​(p.Ser204Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S204N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: ZRSR2 NM_005089.4 missense
• Clinical Significance: Not reported in ClinVar
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.866

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZRSR2	NM_005089.4	c.611G>T	p.Ser204Ile	missense_variant	Exon 8 of 11	ENST00000307771.8	NP_005080.1
ZRSR2	XM_011545589.4	c.680G>T	p.Ser227Ile	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.611G>T	p.Ser204Ile	missense_variant	Exon 8 of 11	1	NM_005089.4	ENSP00000303015.7
ZRSR2	ENST00000684799.1	c.533G>T	p.Ser178Ile	missense_variant	Exon 7 of 11			ENSP00000510773.1
ZRSR2	ENST00000690252.1	n.611G>T		non_coding_transcript_exon_variant	Exon 8 of 13			ENSP00000510140.1
ZRSR2	ENST00000691502.1	n.611G>T		non_coding_transcript_exon_variant	Exon 8 of 13			ENSP00000509336.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.67	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	0.48	D
MutationAssessor	Benign	1.5	L
PhyloP100		6.5
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.53		Loss of disorder (P = 0.0051);
MVP		0.98
MPC		1.3
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.83
gMVP		0.89
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.33		Position offset: -1

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

Other links and lift over

dbSNP: rs1932960051; hg19: chrX-15833853;