X-15815829-T-A

Variant names:

• chrX-15815829-T-A
• rs906630782
• NM_005089.4:c.710T>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_005089.4(ZRSR2):​c.710T>A​(p.Leu237Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000091 in 1,208,719 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000091 (0 hom. 2 hem.)
• Consequence: ZRSR2 NM_005089.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.98
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

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.710T>A	p.Leu237Gln	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.710T>A	p.Leu237Gln	missense	Exon 8 of 11	ENSP00000303015.7	Q15696
	ZRSR2	ENST00000964213.1		c.728T>A	p.Leu243Gln	missense	Exon 8 of 11	ENSP00000634272.1
	ZRSR2	ENST00000964212.1		c.710T>A	p.Leu237Gln	missense	Exon 8 of 11	ENSP00000634271.1

Frequencies

GnomAD3 genomes AF: 0.00000898 AC: 1 AN: 111310 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: 0.00

Gnomad OTH AF: 0.000670

GnomAD2 exomes AF: 0.0000110 AC: 2 AN: 182284 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000245

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000911 AC: 10 AN: 1097409 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 2 AN XY: 362785

African (AFR) AF: 0.00 AC: 0 AN: 26374

American (AMR) AF: 0.00 AC: 0 AN: 35072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19323

East Asian (EAS) AF: 0.00 AC: 0 AN: 30187

South Asian (SAS) AF: 0.00 AC: 0 AN: 53968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40503

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000713 AC: 6 AN: 841792

Other (OTH) AF: 0.0000869 AC: 4 AN: 46053

GnomAD4 genome AF: 0.00000898 AC: 1 AN: 111310 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33466

African (AFR) AF: 0.00 AC: 0 AN: 30576

American (AMR) AF: 0.00 AC: 0 AN: 10433

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3566

South Asian (SAS) AF: 0.00 AC: 0 AN: 2629

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5991

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53050

Other (OTH) AF: 0.000670 AC: 1 AN: 1492

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

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	0.15
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.28	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Uncertain	0.022	D
MutationAssessor	Benign	1.7	L
PhyloP100		6.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.2	N
REVEL	Pathogenic	0.70
Sift	Benign	0.20	T
Sift4G	Benign	0.58	T
Polyphen		1.0	D
Vest4		0.59
MutPred		0.53		Gain of disorder (P = 0.0151)
MVP		0.89
MPC		0.92
ClinPred		0.83	D
GERP RS		4.2
Varity_R		0.64
gMVP		0.67
Mutation Taster		=81/19	polymorphism

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: rs906630782; hg19: chrX-15833952;