rs11704314

Positions:

• chr22-40401929-A-G

Variant summary

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

The NM_015705.6(SGSM3):​c.91-210A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,264 control chromosomes in the GnomAD database, including 1,806 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 0.14 (1806 hom., cov: 33)
• Consequence: SGSM3 NM_015705.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGSM3	NM_015705.6	c.91-210A>G		intron_variant		ENST00000248929.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGSM3	ENST00000248929.14	c.91-210A>G		intron_variant		1	NM_015705.6	P1
SGSM3	ENST00000457767.5	c.-111-210A>G		intron_variant		2
SGSM3	ENST00000485962.5	n.252-210A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20895 AN: 152146 Hom.: 1804 Cov.: 33

Gnomad AFR AF: 0.0588

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.00770

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.137 AC: 20894 AN: 152264 Hom.: 1806 Cov.: 33 AF XY: 0.135 AC XY: 10055 AN XY: 74460

Gnomad4 AFR AF: 0.0586

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.00771

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.133

Alfa AF: 0.160 Hom.: 898

Bravo AF: 0.127

Asia WGS AF: 0.125 AC: 439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.3
DANN	Benign	0.62

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: rs11704314; hg19: chr22-40797933;