rs1590957

chr6-89100692-G-Achr6-89100692-G-T

Variant summary

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

The NM_080743.5(SRSF12):c.417-1745C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 152,130 control chromosomes in the GnomAD database, including 33,318 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 0.65 (33318 hom., cov: 34)
• Consequence: SRSF12 NM_080743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRSF12	NM_080743.5	c.417-1745C>T		intron_variant		ENST00000452027.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRSF12	ENST00000452027.3	c.417-1745C>T		intron_variant		1	NM_080743.5	P1
SRSF12	ENST00000488604.1	n.683-1745C>T		intron_variant, non_coding_transcript_variant		2
SRSF12	ENST00000524221.1	n.699-1745C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99453 AN: 152012 Hom.: 33315 Cov.: 34

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.658

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.654 AC: 99474 AN: 152130 Hom.: 33318 Cov.: 34 AF XY: 0.661 AC XY: 49143 AN XY: 74376

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.678

Gnomad4 ASJ AF: 0.666

Gnomad4 EAS AF: 0.783

Gnomad4 SAS AF: 0.761

Gnomad4 FIN AF: 0.716

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.650

Alfa AF: 0.683 Hom.: 9432

Bravo AF: 0.640

Asia WGS AF: 0.715 AC: 2487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.10
Dann	Benign	0.34

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: rs1590957; hg19: chr6-89810411;