rs713664

Variant names:

• chr22-24831930-T-C
• rs713664
• NM_001098497.3:c.64-12967T>C

Variant summary

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

The NM_001098497.3(SGSM1):​c.64-12967T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,132 control chromosomes in the GnomAD database, including 9,061 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 0.34 (9061 hom., cov: 32)
• Consequence: SGSM1 NM_001098497.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.498
• Publications: 3 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGSM1	NM_001098497.3	c.64-12967T>C		intron_variant	Intron 2 of 24	ENST00000400358.9	NP_001091967.1
SGSM1	NM_001039948.4	c.64-12967T>C		intron_variant	Intron 2 of 25		NP_001035037.1
SGSM1	NM_133454.4	c.64-12967T>C		intron_variant	Intron 2 of 24		NP_597711.1
SGSM1	NM_001098498.3	c.64-12967T>C		intron_variant	Intron 2 of 23		NP_001091968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGSM1	ENST00000400358.9	c.64-12967T>C		intron_variant	Intron 2 of 24	1	NM_001098497.3	ENSP00000383211.4
SGSM1	ENST00000400359.4	c.64-12967T>C		intron_variant	Intron 2 of 25	5		ENSP00000383212.4
SGSM1	ENST00000610372.4	c.64-12967T>C		intron_variant	Intron 2 of 24	5		ENSP00000484682.1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51159 AN: 152014 Hom.: 9067 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.336 AC: 51163 AN: 152132 Hom.: 9061 Cov.: 32 AF XY: 0.337 AC XY: 25043 AN XY: 74382

African (AFR) AF: 0.229 AC: 9518 AN: 41490

American (AMR) AF: 0.384 AC: 5867 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1600 AN: 3468

East Asian (EAS) AF: 0.175 AC: 909 AN: 5184

South Asian (SAS) AF: 0.301 AC: 1450 AN: 4820

European-Finnish (FIN) AF: 0.377 AC: 3987 AN: 10582

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26550 AN: 67978

Other (OTH) AF: 0.361 AC: 763 AN: 2114

Alfa AF: 0.385 Hom.: 19315

Bravo AF: 0.333

Asia WGS AF: 0.250 AC: 873 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	4.6
DANN	Benign	0.63
PhyloP100		0.50
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: rs713664; hg19: chr22-25227897;