9-33051687-T-C

Position:

• chr9-33051687-T-C

Variant summary

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

The NM_018225.3(SMU1):​c.1290+1436A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,226 control chromosomes in the GnomAD database, including 1,323 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 0.12 (1323 hom., cov: 31)
• Consequence: SMU1 NM_018225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.412

Genes affected

SMU1 (HGNC:18247): (SMU1 DNA replication regulator and spliceosomal factor) Involved in mRNA splicing, via spliceosome. Located in nucleus. Part of U2-type precatalytic spliceosome. [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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMU1	NM_018225.3	c.1290+1436A>G		intron_variant		ENST00000397149.4	NP_060695.2
SMU1	XM_005251503.6	c.1137+1436A>G		intron_variant			XP_005251560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMU1	ENST00000397149.4	c.1290+1436A>G		intron_variant		1	NM_018225.3	ENSP00000380336.3

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18872 AN: 152108 Hom.: 1320 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0828

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0702

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.124 AC: 18882 AN: 152226 Hom.: 1323 Cov.: 31 AF XY: 0.125 AC XY: 9303 AN XY: 74440

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.0826

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.0702

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0994

Alfa AF: 0.0927 Hom.: 347

Bravo AF: 0.124

Asia WGS AF: 0.180 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.9
DANN	Benign	0.90

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: rs10813928; hg19: chr9-33051685; COSMIC: COSV68139701;