rs713664

Positions:

• chr22-24831930-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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/exons	MANE	Protein	UniProt
SGSM1	NM_001098497.3	c.64-12967T>C		intron_variant		ENST00000400358.9	NP_001091967.1
SGSM1	NM_001039948.4	c.64-12967T>C		intron_variant			NP_001035037.1
SGSM1	NM_133454.4	c.64-12967T>C		intron_variant			NP_597711.1
SGSM1	NM_001098498.3	c.64-12967T>C		intron_variant			NP_001091968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGSM1	ENST00000400358.9	c.64-12967T>C		intron_variant		1	NM_001098497.3	ENSP00000383211.4
SGSM1	ENST00000400359.4	c.64-12967T>C		intron_variant		5		ENSP00000383212.4
SGSM1	ENST00000610372.4	c.64-12967T>C		intron_variant		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

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.361

Alfa AF: 0.390 Hom.: 15547

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

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: rs713664; hg19: chr22-25227897;