dbSNP rs139719: SGSM1:c.1770+70T>C (chr22-24886798-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001098497.3(SGSM1):c.1770+70T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 1,495,790 control chromosomes in the GnomAD database, including 340,819 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 0.68 ( 35017 hom., cov: 32)

Exomes 𝑓: 0.67 ( 305802 hom. )

Consequence

SGSM1
NM_001098497.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.804

Publications

6 publications found

Variant links:

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]

SGSM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
SGSM1	NM_001098497.3 link	c.1770+70T>C	intron_variant	Intron 16 of 24	ENST00000400358.9	NP_001091967.1
SGSM1	NM_001039948.4 link	c.1935+70T>C	intron_variant	Intron 17 of 25		NP_001035037.1
SGSM1	NM_133454.4 link	c.1935+70T>C	intron_variant	Intron 17 of 24		NP_597711.1
SGSM1	NM_001098498.3 link	c.1770+70T>C	intron_variant	Intron 16 of 23		NP_001091968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGSM1	ENST00000400358.9 link	c.1770+70T>C		intron_variant	Intron 16 of 24	1	NM_001098497.3	ENSP00000383211.4

Frequencies

GnomAD3 genomes

AF:

0.678

AC:

103023

AN:

152016

Hom.:

34967

Cov.:

show subpopulations

Gnomad AFR

AF:

0.667

Gnomad AMI

AF:

0.713

Gnomad AMR

AF:

0.735

Gnomad ASJ

AF:

0.645

Gnomad EAS

AF:

0.625

Gnomad SAS

AF:

0.729

Gnomad FIN

AF:

0.715

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.667

Gnomad OTH

AF:

0.673

GnomAD4 exome

AF:

0.674

AC:

905129

AN:

1343656

Hom.:

305802

AF XY:

0.674

AC XY:

441985

AN XY:

655752

show subpopulations

African (AFR)

AF:

0.667

AC:

20170

AN:

30230

American (AMR)

AF:

0.800

AC:

24359

AN:

30440

Ashkenazi Jewish (ASJ)

AF:

0.629

AC:

13937

AN:

22148

East Asian (EAS)

AF:

0.615

AC:

21555

AN:

35046

South Asian (SAS)

AF:

0.724

AC:

51482

AN:

71114

European-Finnish (FIN)

AF:

0.713

AC:

33986

AN:

47656

Middle Eastern (MID)

AF:

0.620

AC:

3344

AN:

5394

European-Non Finnish (NFE)

AF:

0.668

AC:

699084

AN:

1046144

Other (OTH)

AF:

0.671

AC:

37212

AN:

55484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

14617

29234

43850

58467

73084

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18908

37816

56724

75632

94540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.678

AC:

103128

AN:

152134

Hom.:

35017

Cov.:

AF XY:

0.684

AC XY:

50834

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.668

AC:

27722

AN:

41518

American (AMR)

AF:

0.736

AC:

11230

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.645

AC:

2237

AN:

3470

East Asian (EAS)

AF:

0.626

AC:

3239

AN:

5176

South Asian (SAS)

AF:

0.728

AC:

3506

AN:

4818

European-Finnish (FIN)

AF:

0.715

AC:

7566

AN:

10588

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.667

AC:

45360

AN:

67984

Other (OTH)

AF:

0.676

AC:

1428

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1736

3471

5207

6942

8678

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

812

1624

2436

3248

4060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.669

Hom.:

37114

Bravo

AF:

0.677

Asia WGS

AF:

0.703

AC:

2447

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

1.3

(source)

DANN

Benign

0.51

PhyloP100

-0.80

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over