dbSNP rs2235318: SGSM3:c.367-17C>A (chr22-40404540-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_015705.6(SGSM3):c.367-17C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000246 in 1,611,210 control chromosomes in the GnomAD database, including 2 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 0.0012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 2 hom. )

Consequence

SGSM3
NM_015705.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.93

Publications

8 publications found

Variant links:

Genes affected

SGSM3 (HGNC:25228): (small G protein signaling modulator 3) Enables GTPase activator activity and small GTPase binding activity. Involved in several processes, including Rap protein signal transduction; positive regulation of GTPase activity; and regulation of Rab protein signal transduction. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

SGSM3 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, PanelApp Australia
intellectual disability
Inheritance: AR Classification: LIMITED Submitted by: G2P

SGSM3 links:

ENSG00000284431 (HGNC:):

ENSG00000284431 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015705.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SGSM3	NM_015705.6	MANE Select	c.367-17C>A	intron	N/A	NP_056520.2
SGSM3	NM_001350039.2		c.367-17C>A	intron	N/A	NP_001336968.1
SGSM3	NM_001350040.2		c.367-17C>A	intron	N/A	NP_001336969.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SGSM3	ENST00000248929.14	TSL:1 MANE Select	c.367-17C>A	intron	N/A	ENSP00000248929.8	Q96HU1-1
ENSG00000284431	ENST00000639722.1	TSL:5	n.*1605-17C>A	intron	N/A	ENSP00000492828.1	A0A1W2PRX2
SGSM3	ENST00000956266.1		c.367-17C>A	intron	N/A	ENSP00000626325.1

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

180

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00399

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.000286

AC:

AN:

248436

AF XY:

0.000194

show subpopulations

Gnomad AFR exome

AF:

0.00344

Gnomad AMR exome

AF:

0.000175

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000714

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.000149

AC:

217

AN:

1459040

Hom.:

Cov.:

AF XY:

0.000141

AC XY:

102

AN XY:

725848

show subpopulations

African (AFR)

AF:

0.00455

AC:

152

AN:

33396

American (AMR)

AF:

0.000270

AC:

AN:

44516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39618

South Asian (SAS)

AF:

0.00

AC:

AN:

86076

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53278

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000171

AC:

AN:

1109990

Other (OTH)

AF:

0.000514

AC:

AN:

60286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00118

AC:

179

AN:

152170

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.00395

AC:

164

AN:

41522

American (AMR)

AF:

0.000458

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67994

Other (OTH)

AF:

0.00190

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000215

Hom.:

319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

(source)

DANN

Benign

0.47

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.48

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.48

Position offset: 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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over