rs17001868

Positions:

• chr22-40382227-A-C
• chr22-40382227-A-G

Variant summary

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

The ENST00000248929.14(SGSM3):​c.-112+11539A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,176 control chromosomes in the GnomAD database, including 2,018 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 0.13 (2018 hom., cov: 32)
• Consequence: SGSM3 ENST00000248929.14 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174

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]

SGSM3-AS1 (HGNC:41088): (SGSM3 antisense RNA 1)

ADSL (HGNC:291): (adenylosuccinate lyase) The protein encoded by this gene belongs to the lyase 1 family. It is an essential enzyme involved in purine metabolism, and catalyzes two non-sequential reactions in the de novo purine biosynthetic pathway: the conversion of succinylaminoimidazole carboxamide ribotide (SAICAR) to aminoimidazole carboxamide ribotide (AICAR) and the conversion of adenylosuccinate (S-AMP) to adenosine monophosphate (AMP). Mutations in this gene are associated with adenylosuccinase deficiency (ADSLD), a disorder marked with psychomotor retardation, epilepsy or autistic features. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGSM3	NM_015705.6	c.-112+11539A>C		intron_variant		ENST00000248929.14	NP_056520.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGSM3	ENST00000248929.14	c.-112+11539A>C		intron_variant		1	NM_015705.6	ENSP00000248929	P1
SGSM3-AS1	ENST00000414261.1	n.146+5918T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19177 AN: 152058 Hom.: 2012 Cov.: 32

Gnomad AFR AF: 0.0293

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.0721

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.126 AC: 19191 AN: 152176 Hom.: 2018 Cov.: 32 AF XY: 0.135 AC XY: 10013 AN XY: 74388

Gnomad4 AFR AF: 0.0292

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.0721

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.117

Alfa AF: 0.129 Hom.: 2624

Bravo AF: 0.137

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.68

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: rs17001868; hg19: chr22-40778231;