22-24850283-A-C

Position:

• chr22-24850283-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001098497.3(SGSM1):​c.306A>C​(p.Arg102Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SGSM1 NM_001098497.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38

Genes affected

SGSM1 (HGNC:29410): (small G protein signaling modulator 1) Enables GTPase activator activity and small GTPase binding activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Located in cytoplasmic vesicle membrane and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31722242).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGSM1	NM_001098497.3	c.306A>C	p.Arg102Ser	missense_variant	5/25	ENST00000400358.9	NP_001091967.1
SGSM1	NM_001039948.4	c.306A>C	p.Arg102Ser	missense_variant	5/26		NP_001035037.1
SGSM1	NM_133454.4	c.306A>C	p.Arg102Ser	missense_variant	5/25		NP_597711.1
SGSM1	NM_001098498.3	c.306A>C	p.Arg102Ser	missense_variant	5/24		NP_001091968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGSM1	ENST00000400358.9	c.306A>C	p.Arg102Ser	missense_variant	5/25	1	NM_001098497.3	ENSP00000383211.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2023

The c.306A>C (p.R102S) alteration is located in exon 5 (coding exon 5) of the SGSM1 gene. This alteration results from a A to C substitution at nucleotide position 306, causing the arginine (R) at amino acid position 102 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.000067	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	.;.;T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	.;M;M
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.1	.;D;D
REVEL	Benign	0.17
Sift	Benign	0.11	.;T;T
Sift4G	Benign	0.10	T;T;T
Polyphen		0.97, 0.98	.;D;D
Vest4		0.48
MutPred		0.45		Loss of catalytic residue at R102 (P = 0.0356);Loss of catalytic residue at R102 (P = 0.0356);Loss of catalytic residue at R102 (P = 0.0356);
MVP		0.12
MPC		0.41
ClinPred		0.95	D
GERP RS		2.7
Varity_R		0.46
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-25246250;