rs6968355

Variant names:

• chr7-105117803-T-C
• rs6968355
• NM_182692.3:c.*35A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000393651.8(SRPK2):​c.*35A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,607,548 control chromosomes in the GnomAD database, including 30,542 homozygotes. 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: 𝑓 0.14 (2053 hom., cov: 33)
  • Exomes 𝑓: 0.19 (28489 hom.)
• Consequence: SRPK2 ENST00000393651.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.756
• Publications: 8 publications found

Genes affected

SRPK2 (HGNC:11306): (SRSF protein kinase 2) Enables ATP binding activity; magnesium ion binding activity; and protein serine/threonine kinase activity. Involved in several processes, including nucleic acid metabolic process; peptidyl-serine phosphorylation; and regulation of viral genome replication. Located in chromatin; cytosol; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393651.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRPK2	NM_182692.3	MANE Select	c.*35A>G		3_prime_UTR	Exon 16 of 16	NP_872634.1
	SRPK2	NM_001350740.2		c.*35A>G		3_prime_UTR	Exon 16 of 16	NP_001337669.1
	SRPK2	NM_001350741.2		c.*35A>G		3_prime_UTR	Exon 17 of 17	NP_001337670.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRPK2	ENST00000393651.8	TSL:2 MANE Select	c.*35A>G		3_prime_UTR	Exon 16 of 16	ENSP00000377262.3
	SRPK2	ENST00000357311.7	TSL:1	c.*35A>G		3_prime_UTR	Exon 15 of 15	ENSP00000349863.3
	SRPK2	ENST00000489828.5	TSL:1	c.*35A>G		3_prime_UTR	Exon 17 of 17	ENSP00000419791.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21648 AN: 152154 Hom.: 2054 Cov.: 33

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.141

GnomAD2 exomes AF: 0.181 AC: 45067 AN: 248928 AF XY: 0.181

Gnomad AFR exome AF: 0.0297

Gnomad AMR exome AF: 0.322

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.000987

Gnomad FIN exome AF: 0.213

Gnomad NFE exome AF: 0.184

Gnomad OTH exome AF: 0.175

GnomAD4 exome AF: 0.190 AC: 276711 AN: 1455276 Hom.: 28489 Cov.: 29 AF XY: 0.191 AC XY: 138265 AN XY: 724176

African (AFR) AF: 0.0278 AC: 925 AN: 33290

American (AMR) AF: 0.307 AC: 13671 AN: 44560

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 3404 AN: 26088

East Asian (EAS) AF: 0.00103 AC: 41 AN: 39618

South Asian (SAS) AF: 0.200 AC: 17168 AN: 86014

European-Finnish (FIN) AF: 0.210 AC: 11165 AN: 53180

Middle Eastern (MID) AF: 0.111 AC: 462 AN: 4144

European-Non Finnish (NFE) AF: 0.198 AC: 219401 AN: 1108324

Other (OTH) AF: 0.174 AC: 10474 AN: 60058

GnomAD4 genome AF: 0.142 AC: 21644 AN: 152272 Hom.: 2053 Cov.: 33 AF XY: 0.144 AC XY: 10701 AN XY: 74450

African (AFR) AF: 0.0360 AC: 1498 AN: 41566

American (AMR) AF: 0.211 AC: 3225 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 480 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5190

South Asian (SAS) AF: 0.186 AC: 897 AN: 4828

European-Finnish (FIN) AF: 0.216 AC: 2284 AN: 10586

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12835 AN: 68012

Other (OTH) AF: 0.139 AC: 293 AN: 2112

Alfa AF: 0.159 Hom.: 1780

Bravo AF: 0.138

Asia WGS AF: 0.0770 AC: 267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	10
DANN	Benign	0.77
PhyloP100		0.76
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: rs6968355; hg19: chr7-104758250; COSMIC: COSV57581065; COSMIC: COSV57581065;