chr22-24823963-T-C

Position:

• chr22-24823963-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.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

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=-0.79).
• 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/exons	MANE	Protein	UniProt
SGSM1	NM_001098497.3	c.63+17479T>C		intron_variant		ENST00000400358.9	NP_001091967.1
SGSM1	NM_001039948.4	c.63+17479T>C		intron_variant			NP_001035037.1
SGSM1	NM_001098498.3	c.63+17479T>C		intron_variant			NP_001091968.1
SGSM1	NM_133454.4	c.63+17479T>C		intron_variant			NP_597711.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGSM1	ENST00000400358.9	c.63+17479T>C		intron_variant		1	NM_001098497.3	ENSP00000383211	P3
SGSM1	ENST00000400359.4	c.63+17479T>C		intron_variant		5		ENSP00000383212	A1
SGSM1	ENST00000610372.4	c.63+17479T>C		intron_variant		5		ENSP00000484682

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

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.682

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.343

Alfa AF: 0.350 Hom.: 9792

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

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: rs2330929; hg19: chr22-25219930;