rs139719

Positions:

• chr22-24886798-T-C

Variant summary

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

The NM_001098497.3(SGSM1):​c.1770+70T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 1,495,790 control chromosomes in the GnomAD database, including 340,819 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 0.68 (35017 hom., cov: 32)
  • Exomes 𝑓: 0.67 (305802 hom.)
• Consequence: SGSM1 NM_001098497.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.804

Genes affected

SGSM1 (HGNC:29410): (small G protein signaling modulator 1) Enables GTPase activator activity and small GTPase binding activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Located in cytoplasmic vesicle membrane and cytosol. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGSM1	NM_001098497.3	c.1770+70T>C		intron_variant		ENST00000400358.9
SGSM1	NM_001039948.4	c.1935+70T>C		intron_variant
SGSM1	NM_001098498.3	c.1770+70T>C		intron_variant
SGSM1	NM_133454.4	c.1935+70T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGSM1	ENST00000400358.9	c.1770+70T>C		intron_variant		1	NM_001098497.3	P3

Frequencies

GnomAD3 genomes AF: 0.678 AC: 103023 AN: 152016 Hom.: 34967 Cov.: 32

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.673

GnomAD4 exome AF: 0.674 AC: 905129 AN: 1343656 Hom.: 305802 AF XY: 0.674 AC XY: 441985 AN XY: 655752

Gnomad4 AFR exome AF: 0.667

Gnomad4 AMR exome AF: 0.800

Gnomad4 ASJ exome AF: 0.629

Gnomad4 EAS exome AF: 0.615

Gnomad4 SAS exome AF: 0.724

Gnomad4 FIN exome AF: 0.713

Gnomad4 NFE exome AF: 0.668

Gnomad4 OTH exome AF: 0.671

GnomAD4 genome AF: 0.678 AC: 103128 AN: 152134 Hom.: 35017 Cov.: 32 AF XY: 0.684 AC XY: 50834 AN XY: 74370

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.736

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.626

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.715

Gnomad4 NFE AF: 0.667

Gnomad4 OTH AF: 0.676

Alfa AF: 0.670 Hom.: 31621

Bravo AF: 0.677

Asia WGS AF: 0.703 AC: 2447 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	1.3
DANN	Benign	0.51

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: rs139719; hg19: chr22-25282765; COSMIC: COSV68509365;