rs6938490

Positions:

• chr6-89096511-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080743.5(SRSF12):​c.*2067C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,062 control chromosomes in the GnomAD database, including 5,483 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 0.26 (5483 hom., cov: 33)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: SRSF12 NM_080743.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73

Genes affected

SRSF12 (HGNC:21220): (serine and arginine rich splicing factor 12) Enables RNA binding activity. Involved in mRNA 5'-splice site recognition and regulation of alternative mRNA splicing, via spliceosome. Predicted to be located in nucleoplasm. Predicted to be active in cytoplasm and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

PM20D2 (HGNC:21408): (peptidase M20 domain containing 2) Enables dipeptidase activity and identical protein binding activity. Acts upstream of or within proteolysis and regulation of cellular protein metabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRSF12	NM_080743.5	c.*2067C>T		3_prime_UTR_variant	5/5	ENST00000452027.3	NP_542781.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRSF12	ENST00000452027.3	c.*2067C>T		3_prime_UTR_variant	5/5	1	NM_080743.5	ENSP00000414302.2

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39488 AN: 151938 Hom.: 5483 Cov.: 33

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.0986

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 NFE exome AF: 0.333

GnomAD4 genome AF: 0.260 AC: 39489 AN: 152056 Hom.: 5483 Cov.: 33 AF XY: 0.257 AC XY: 19080 AN XY: 74334

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.0984

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.287

Alfa AF: 0.286 Hom.: 1909

Bravo AF: 0.253

Asia WGS AF: 0.225 AC: 783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.7
DANN	Benign	0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs6938490; hg19: chr6-89806230;