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GeneBe

22-40405203-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_015705.6(SGSM3):c.537C>T(p.Ile179=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00045 in 1,589,130 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00068 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00043 ( 6 hom. )

Consequence

SGSM3
NM_015705.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.50
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-40405203-C-T is Benign according to our data. Variant chr22-40405203-C-T is described in ClinVar as [Benign]. Clinvar id is 738918.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.5 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000676 (103/152332) while in subpopulation EAS AF= 0.0184 (95/5172). AF 95% confidence interval is 0.0154. There are 2 homozygotes in gnomad4. There are 70 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SGSM3NM_015705.6 linkuse as main transcriptc.537C>T p.Ile179= synonymous_variant 7/22 ENST00000248929.14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SGSM3ENST00000248929.14 linkuse as main transcriptc.537C>T p.Ile179= synonymous_variant 7/221 NM_015705.6 P1Q96HU1-1
SGSM3ENST00000457767.5 linkuse as main transcriptc.336C>T p.Ile112= synonymous_variant 6/82
SGSM3ENST00000478085.5 linkuse as main transcriptn.514C>T non_coding_transcript_exon_variant 3/92
SGSM3ENST00000485962.5 linkuse as main transcriptn.698C>T non_coding_transcript_exon_variant 7/205

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000677
AC:
103
AN:
152214
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0183
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000958
GnomAD3 exomes
AF:
0.00137
AC:
318
AN:
232284
Hom.:
4
AF XY:
0.00122
AC XY:
154
AN XY:
126652
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0188
Gnomad SAS exome
AF:
0.000317
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000947
Gnomad OTH exome
AF:
0.000180
GnomAD4 exome
AF:
0.000426
AC:
612
AN:
1436798
Hom.:
6
Cov.:
31
AF XY:
0.000405
AC XY:
289
AN XY:
713254
show subpopulations
Gnomad4 AFR exome
AF:
0.0000308
Gnomad4 AMR exome
AF:
0.0000481
Gnomad4 ASJ exome
AF:
0.0000397
Gnomad4 EAS exome
AF:
0.0145
Gnomad4 SAS exome
AF:
0.000119
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000200
Gnomad4 OTH exome
AF:
0.000389
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000676
AC:
103
AN:
152332
Hom.:
2
Cov.:
33
AF XY:
0.000940
AC XY:
70
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0184
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000948
Alfa
AF:
0.000155
Hom.:
0
Bravo
AF:
0.000880
Asia WGS
AF:
0.00491
AC:
17
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 02, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
Cadd
Benign
6.5
Dann
Benign
0.86
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs150525363; hg19: chr22-40801207; API