22-24823963-T-C

Variant names:

• chr22-24823963-T-C
• rs2330929
• NM_001098497.3:c.63+17479T>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.63+17479T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,124 control chromosomes in the GnomAD database, including 9,317 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 (9317 hom., cov: 32)
• Consequence: SGSM1 NM_001098497.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.55
• Publications: 2 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGSM1	NM_001098497.3	c.63+17479T>C		intron_variant	Intron 2 of 24	ENST00000400358.9	NP_001091967.1
SGSM1	NM_001039948.4	c.63+17479T>C		intron_variant	Intron 2 of 25		NP_001035037.1
SGSM1	NM_133454.4	c.63+17479T>C		intron_variant	Intron 2 of 24		NP_597711.1
SGSM1	NM_001098498.3	c.63+17479T>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.63+17479T>C		intron_variant	Intron 2 of 24	1	NM_001098497.3	ENSP00000383211.4
SGSM1	ENST00000400359.4	c.63+17479T>C		intron_variant	Intron 2 of 25	5		ENSP00000383212.4
SGSM1	ENST00000610372.4	c.63+17479T>C		intron_variant	Intron 2 of 24	5		ENSP00000484682.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51583 AN: 152006 Hom.: 9312 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.339 AC: 51612 AN: 152124 Hom.: 9317 Cov.: 32 AF XY: 0.342 AC XY: 25448 AN XY: 74384

African (AFR) AF: 0.250 AC: 10365 AN: 41462

American (AMR) AF: 0.371 AC: 5664 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1410 AN: 3466

East Asian (EAS) AF: 0.682 AC: 3534 AN: 5184

South Asian (SAS) AF: 0.308 AC: 1486 AN: 4826

European-Finnish (FIN) AF: 0.397 AC: 4209 AN: 10594

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23804 AN: 67992

Other (OTH) AF: 0.343 AC: 726 AN: 2114

Alfa AF: 0.349 Hom.: 11571

Bravo AF: 0.337

Asia WGS AF: 0.488 AC: 1698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.39
DANN	Benign	0.87
PhyloP100		-2.6
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: rs2330929; hg19: chr22-25219930;