NM_015705.6:c.537C>A

Variant names:

• chr22-40405203-C-A
• rs150525363
• NM_015705.6:c.537C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_015705.6(SGSM3):​c.537C>A​(p.Ile179Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I179I) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SGSM3 NM_015705.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=-1.5 with no splicing effect.

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.537C>A	p.Ile179Ile	synonymous	Exon 7 of 22	NP_056520.2
	SGSM3	NM_001350039.2		c.537C>A	p.Ile179Ile	synonymous	Exon 7 of 22	NP_001336968.1
	SGSM3	NM_001350040.2		c.537C>A	p.Ile179Ile	synonymous	Exon 7 of 22	NP_001336969.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGSM3	ENST00000248929.14	TSL:1 MANE Select	c.537C>A	p.Ile179Ile	synonymous	Exon 7 of 22	ENSP00000248929.8	Q96HU1-1
	ENSG00000284431	ENST00000639722.1	TSL:5	n.*1775C>A		non_coding_transcript_exon	Exon 18 of 31	ENSP00000492828.1	A0A1W2PRX2
	ENSG00000284431	ENST00000639722.1	TSL:5	n.*1775C>A		3_prime_UTR	Exon 18 of 31	ENSP00000492828.1	A0A1W2PRX2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436806 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 713258

African (AFR) AF: 0.00 AC: 0 AN: 32430

American (AMR) AF: 0.00 AC: 0 AN: 41602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25168

East Asian (EAS) AF: 0.00 AC: 0 AN: 38188

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 83932

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098602

Other (OTH) AF: 0.00 AC: 0 AN: 59126

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	2.2
DANN	Benign	0.84
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs150525363; hg19: chr22-40801207;