6-89100692-G-A

Variant names:

• chr6-89100692-G-A
• rs1590957
• NM_080743.5:c.417-1745C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080743.5. 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
	SRSF12	NM_080743.5	MANE Select	c.417-1745C>T		intron	N/A	NP_542781.3
	SRSF12	NM_001376896.1		c.132-1745C>T		intron	N/A	NP_001363825.1
	SRSF12	NM_001376897.1		c.132-1745C>T		intron	N/A	NP_001363826.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF12	ENST00000452027.3	TSL:1 MANE Select	c.417-1745C>T		intron	N/A	ENSP00000414302.2
	SRSF12	ENST00000488604.1	TSL:2	n.683-1745C>T		intron	N/A
	SRSF12	ENST00000524221.1	TSL:2	n.699-1745C>T		intron	N/A

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

African (AFR) AF: 0.498 AC: 20642 AN: 41488

American (AMR) AF: 0.678 AC: 10368 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 2314 AN: 3472

East Asian (EAS) AF: 0.783 AC: 4064 AN: 5190

South Asian (SAS) AF: 0.761 AC: 3674 AN: 4828

European-Finnish (FIN) AF: 0.716 AC: 7564 AN: 10560

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48594 AN: 67980

Other (OTH) AF: 0.650 AC: 1374 AN: 2114

Alfa AF: 0.645 Hom.: 18882

Bravo AF: 0.640

Asia WGS AF: 0.715 AC: 2487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.10
DANN	Benign	0.34
PhyloP100		-0.20
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: rs1590957; hg19: chr6-89810411;