17-2379485-G-A

Variant names:

• chr17-2379485-G-A
• rs61741902
• NM_014853.3:c.3121G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014853.3(SGSM2):​c.3121G>A​(p.Val1041Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,613,586 control chromosomes in the GnomAD database, including 127 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 0.0090 (9 hom., cov: 33)
  • Exomes 𝑓: 0.012 (118 hom.)
• Consequence: SGSM2 NM_014853.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.12
• Publications: 14 publications found

Genes affected

SGSM2 (HGNC:29026): (small G protein signaling modulator 2) The protein encoded by this gene is a GTPase activator with activity towards RAB32 and RAB33B, which are regulators of membrane trafficking. The encoded protein inactivates RAB32 and can bind RAB9A-GTP, a protein required for RAB32 activation. [provided by RefSeq, Oct 2016]

SGSM2-AS1 (HGNC:56091): (SGSM2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007389635).
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014853.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGSM2	NM_014853.3	MANE Select	c.3121G>A	p.Val1041Ile	missense	Exon 24 of 24	NP_055668.2
	SGSM2	NM_001098509.2		c.2986G>A	p.Val996Ile	missense	Exon 23 of 23	NP_001091979.1
	SGSM2	NM_001346700.2		c.2932+282G>A		intron	N/A	NP_001333629.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGSM2	ENST00000268989.8	TSL:1 MANE Select	c.3121G>A	p.Val1041Ile	missense	Exon 24 of 24	ENSP00000268989.3
	SGSM2	ENST00000426855.6	TSL:1	c.2986G>A	p.Val996Ile	missense	Exon 23 of 23	ENSP00000415107.2
	SGSM2	ENST00000572925.1	TSL:3	c.88G>A	p.Val30Ile	missense	Exon 2 of 3	ENSP00000461820.2

Frequencies

GnomAD3 genomes AF: 0.00901 AC: 1372 AN: 152192 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.00265

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.00804

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00703

Gnomad FIN AF: 0.0117

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.0102 AC: 2567 AN: 250844 AF XY: 0.0102

Gnomad AFR exome AF: 0.00216

Gnomad AMR exome AF: 0.00619

Gnomad ASJ exome AF: 0.0135

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0154

Gnomad NFE exome AF: 0.0130

Gnomad OTH exome AF: 0.0126

GnomAD4 exome AF: 0.0122 AC: 17798 AN: 1461276 Hom.: 118 Cov.: 32 AF XY: 0.0122 AC XY: 8857 AN XY: 726854

African (AFR) AF: 0.00188 AC: 63 AN: 33476

American (AMR) AF: 0.00615 AC: 275 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 341 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0103 AC: 892 AN: 86234

European-Finnish (FIN) AF: 0.0141 AC: 749 AN: 53148

Middle Eastern (MID) AF: 0.00573 AC: 33 AN: 5764

European-Non Finnish (NFE) AF: 0.0134 AC: 14872 AN: 1111724

Other (OTH) AF: 0.00949 AC: 573 AN: 60390

GnomAD4 genome AF: 0.00901 AC: 1372 AN: 152310 Hom.: 9 Cov.: 33 AF XY: 0.00850 AC XY: 633 AN XY: 74472

African (AFR) AF: 0.00265 AC: 110 AN: 41560

American (AMR) AF: 0.00803 AC: 123 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00704 AC: 34 AN: 4830

European-Finnish (FIN) AF: 0.0117 AC: 124 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0131 AC: 894 AN: 68020

Other (OTH) AF: 0.00758 AC: 16 AN: 2112

Alfa AF: 0.0112 Hom.: 16

Bravo AF: 0.00827

TwinsUK AF: 0.0159 AC: 59

ALSPAC AF: 0.0148 AC: 57

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.0138 AC: 119

ExAC AF: 0.00988 AC: 1199

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.0118

EpiControl AF: 0.0119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
MetaRNN	Benign	0.0074	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	M
PhyloP100		8.1
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.28
Sift	Benign	0.054	T
Sift4G	Uncertain	0.053	T
Polyphen		0.34	B
Vest4		0.25
MPC		0.13
ClinPred		0.024	T
GERP RS		5.3
PromoterAI		0.052	Neutral
Varity_R		0.18
gMVP		0.38
Mutation Taster		=63/37	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs61741902; hg19: chr17-2282779; COSMIC: COSV51512833; COSMIC: COSV51512833;