rs11704314

Variant names:

• chr22-40401929-A-G
• rs11704314
• NM_015705.6:c.91-210A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, PanelApp Australia
• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ENSG00000284431 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015705.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGSM3	NM_015705.6	MANE Select	c.91-210A>G		intron	N/A	NP_056520.2
	SGSM3	NM_001350039.2		c.91-210A>G		intron	N/A	NP_001336968.1
	SGSM3	NM_001350040.2		c.91-210A>G		intron	N/A	NP_001336969.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGSM3	ENST00000248929.14	TSL:1 MANE Select	c.91-210A>G		intron	N/A	ENSP00000248929.8	Q96HU1-1
	ENSG00000284431	ENST00000639722.1	TSL:5	n.*1329-210A>G		intron	N/A	ENSP00000492828.1	A0A1W2PRX2
	SGSM3	ENST00000956266.1		c.91-210A>G		intron	N/A	ENSP00000626325.1

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

African (AFR) AF: 0.0586 AC: 2435 AN: 41552

American (AMR) AF: 0.117 AC: 1787 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 662 AN: 3472

East Asian (EAS) AF: 0.00771 AC: 40 AN: 5186

South Asian (SAS) AF: 0.292 AC: 1408 AN: 4820

European-Finnish (FIN) AF: 0.135 AC: 1435 AN: 10608

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12684 AN: 68014

Other (OTH) AF: 0.133 AC: 282 AN: 2116

Alfa AF: 0.157 Hom.: 1399

Bravo AF: 0.127

Asia WGS AF: 0.125 AC: 439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.3
DANN	Benign	0.62
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11704314; hg19: chr22-40797933;