22-40404540-C-T

Position:

• chr22-40404540-C-T

Variant summary

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

The NM_015705.6(SGSM3):​c.367-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,610,760 control chromosomes in the GnomAD database, including 33,154 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 0.19 (3236 hom., cov: 33)
  • Exomes 𝑓: 0.19 (29918 hom.)
• Consequence: SGSM3 NM_015705.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

Genes affected

SGSM3 (HGNC:25228): (small G protein signaling modulator 3) Enables GTPase activator activity and small GTPase binding activity. Involved in several processes, including Rap protein signal transduction; positive regulation of GTPase activity; and regulation of Rab protein signal transduction. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000284431 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGSM3	NM_015705.6	c.367-17C>T		intron_variant		ENST00000248929.14	NP_056520.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGSM3	ENST00000248929.14	c.367-17C>T		intron_variant		1	NM_015705.6	ENSP00000248929.8
ENSG00000284431	ENST00000639722.1	n.*1605-17C>T		intron_variant		5		ENSP00000492828.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28439 AN: 152006 Hom.: 3226 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.171

GnomAD3 exomes AF: 0.225 AC: 56006 AN: 248436 Hom.: 9009 AF XY: 0.211 AC XY: 28383 AN XY: 134358

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.552

Gnomad ASJ exome AF: 0.0956

Gnomad EAS exome AF: 0.182

Gnomad SAS exome AF: 0.137

Gnomad FIN exome AF: 0.220

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.199

GnomAD4 exome AF: 0.188 AC: 274108 AN: 1458636 Hom.: 29918 Cov.: 31 AF XY: 0.185 AC XY: 134494 AN XY: 725644

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.530

Gnomad4 ASJ exome AF: 0.0992

Gnomad4 EAS exome AF: 0.261

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.179

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.187 AC: 28478 AN: 152124 Hom.: 3236 Cov.: 33 AF XY: 0.193 AC XY: 14324 AN XY: 74372

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.170

Alfa AF: 0.119 Hom.: 313

Bravo AF: 0.200

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.071
DANN	Benign	0.41

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: rs2235318; hg19: chr22-40800544; COSMIC: COSV50651651; COSMIC: COSV50651651;