NM_015705.6:c.511G>C

Variant names:

• chr22-40405177-G-C
• rs144524421
• NM_015705.6:c.511G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015705.6(SGSM3):​c.511G>C​(p.Ala171Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000255 in 1,571,610 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SGSM3 NM_015705.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.56

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]

ENSG00000284431 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGSM3	NM_015705.6	c.511G>C	p.Ala171Pro	missense_variant	Exon 7 of 22	ENST00000248929.14	NP_056520.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGSM3	ENST00000248929.14	c.511G>C	p.Ala171Pro	missense_variant	Exon 7 of 22	1	NM_015705.6	ENSP00000248929.8
ENSG00000284431	ENST00000639722.1	n.*1749G>C		non_coding_transcript_exon_variant	Exon 18 of 31	5		ENSP00000492828.1
ENSG00000284431	ENST00000639722.1	n.*1749G>C		3_prime_UTR_variant	Exon 18 of 31	5		ENSP00000492828.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1419462 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 703962

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.17e-7

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152148 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74328

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.082	T;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.80	.;N
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Uncertain	0.39
Sift	Benign	0.066	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.037	.;B
Vest4		0.89
MutPred		0.66		.;Loss of MoRF binding (P = 0.1021);
MVP		0.44
MPC		0.74
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.88
gMVP		0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs144524421; hg19: chr22-40801181;