17-2375776-C-A

Variant names:

• chr17-2375776-C-A
• NM_014853.3:c.2385C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014853.3(SGSM2):​c.2385C>A​(p.His795Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SGSM2 NM_014853.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.117
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059583336).

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.2385C>A	p.His795Gln	missense	Exon 18 of 24	NP_055668.2	O43147-2
	SGSM2	NM_001098509.2		c.2250C>A	p.His750Gln	missense	Exon 17 of 23	NP_001091979.1	O43147-1
	SGSM2	NM_001346700.2		c.2250C>A	p.His750Gln	missense	Exon 17 of 23	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.2385C>A	p.His795Gln	missense	Exon 18 of 24	ENSP00000268989.3	O43147-2
	SGSM2	ENST00000426855.6	TSL:1	c.2250C>A	p.His750Gln	missense	Exon 17 of 23	ENSP00000415107.2	O43147-1
	SGSM2	ENST00000968832.1		c.2388C>A	p.His796Gln	missense	Exon 18 of 24	ENSP00000638891.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.35
DANN	Benign	0.74
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.060	N
PhyloP100		-0.12
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.048
Sift	Benign	0.32	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.099
MutPred		0.23		Gain of helix (P = 0.0078)
MVP		0.085
MPC		0.13
ClinPred		0.073	T
GERP RS		0.66
Varity_R		0.033
gMVP		0.21

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

hg19: chr17-2279070;