rs12451892

Positions:

• chr17-2344688-T-C

Variant summary

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

The NM_014853.3(SGSM2):​c.133+1068T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,956 control chromosomes in the GnomAD database, including 14,944 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 (14944 hom., cov: 32)
• Consequence: SGSM2 NM_014853.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.962

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

Verdict is Benign. Variant got -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 = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGSM2	NM_014853.3	c.133+1068T>C		intron_variant		ENST00000268989.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGSM2	ENST00000268989.8	c.133+1068T>C		intron_variant		1	NM_014853.3	P4

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66207 AN: 151838 Hom.: 14932 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.436 AC: 66279 AN: 151956 Hom.: 14944 Cov.: 32 AF XY: 0.436 AC XY: 32365 AN XY: 74266

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.443

Alfa AF: 0.390 Hom.: 16224

Bravo AF: 0.452

Asia WGS AF: 0.359 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.49
DANN	Benign	0.39

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: rs12451892; hg19: chr17-2247982;