NM_005089.4:c.254A>C

Variant names:

• chrX-15803738-A-C
• rs368125859
• NM_005089.4:c.254A>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_005089.4(ZRSR2):​c.254A>C​(p.Glu85Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000075 in 1,199,910 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.0000037 (0 hom. 2 hem.)
• Consequence: ZRSR2 NM_005089.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.15
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.046478957).
• 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.254A>C	p.Glu85Ala	missense	Exon 4 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.254A>C	p.Glu85Ala	missense	Exon 4 of 11	ENSP00000303015.7	Q15696
	ZRSR2	ENST00000964213.1		c.254A>C	p.Glu85Ala	missense	Exon 4 of 11	ENSP00000634272.1
	ZRSR2	ENST00000964212.1		c.254A>C	p.Glu85Ala	missense	Exon 4 of 11	ENSP00000634271.1

Frequencies

GnomAD3 genomes AF: 0.0000451 AC: 5 AN: 110934 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00140

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000121 AC: 2 AN: 165742 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000155

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000367 AC: 4 AN: 1088923 Hom.: 0 Cov.: 30 AF XY: 0.00000562 AC XY: 2 AN XY: 356101

African (AFR) AF: 0.00 AC: 0 AN: 26196

American (AMR) AF: 0.00 AC: 0 AN: 34318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19235

East Asian (EAS) AF: 0.0000334 AC: 1 AN: 29942

South Asian (SAS) AF: 0.0000190 AC: 1 AN: 52503

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40033

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4127

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 836777

Other (OTH) AF: 0.0000437 AC: 2 AN: 45792

GnomAD4 genome AF: 0.0000451 AC: 5 AN: 110987 Hom.: 0 Cov.: 22 AF XY: 0.0000301 AC XY: 1 AN XY: 33173

African (AFR) AF: 0.00 AC: 0 AN: 30551

American (AMR) AF: 0.00 AC: 0 AN: 10259

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

East Asian (EAS) AF: 0.00140 AC: 5 AN: 3571

South Asian (SAS) AF: 0.00 AC: 0 AN: 2637

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5857

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 215

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53056

Other (OTH) AF: 0.00 AC: 0 AN: 1506

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000165 AC: 2

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	0.097
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.1
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.14
Sift	Benign	0.030	D
Sift4G	Uncertain	0.054	T
Polyphen		0.23	B
Vest4		0.27
MutPred		0.15		Gain of MoRF binding (P = 0.0587)
MVP		0.31
MPC		0.43
ClinPred		0.98	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.66
gMVP		0.36
Mutation Taster		=66/34	polymorphism

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

Other links and lift over

dbSNP: rs368125859; hg19: chrX-15821861;