17-2359409-C-T

Variant names:

• chr17-2359409-C-T
• rs4790333
• NM_014853.3:c.134-2228C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014853.3(SGSM2):​c.134-2228C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,888 control chromosomes in the GnomAD database, including 15,383 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 0.44 (15383 hom., cov: 31)
• Consequence: SGSM2 NM_014853.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 40 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGSM2	NM_014853.3	MANE Select	c.134-2228C>T		intron	N/A	NP_055668.2	O43147-2
	SGSM2	NM_001098509.2		c.134-2228C>T		intron	N/A	NP_001091979.1	O43147-1
	SGSM2	NM_001346700.2		c.134-2228C>T		intron	N/A	NP_001333629.1	O43147-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGSM2	ENST00000268989.8	TSL:1 MANE Select	c.134-2228C>T		intron	N/A	ENSP00000268989.3	O43147-2
	SGSM2	ENST00000426855.6	TSL:1	c.134-2228C>T		intron	N/A	ENSP00000415107.2	O43147-1
	SGSM2	ENST00000968832.1		c.272-2228C>T		intron	N/A	ENSP00000638891.1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67058 AN: 151772 Hom.: 15378 Cov.: 31

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.442 AC: 67095 AN: 151888 Hom.: 15383 Cov.: 31 AF XY: 0.449 AC XY: 33315 AN XY: 74242

African (AFR) AF: 0.383 AC: 15865 AN: 41404

American (AMR) AF: 0.351 AC: 5353 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1608 AN: 3464

East Asian (EAS) AF: 0.750 AC: 3867 AN: 5154

South Asian (SAS) AF: 0.650 AC: 3133 AN: 4818

European-Finnish (FIN) AF: 0.523 AC: 5519 AN: 10546

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30321 AN: 67930

Other (OTH) AF: 0.407 AC: 858 AN: 2110

Alfa AF: 0.446 Hom.: 36956

Bravo AF: 0.421

Asia WGS AF: 0.667 AC: 2318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.55
PhyloP100		-0.20
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: rs4790333; hg19: chr17-2262703;