22-40401643-T-C
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_015705.6(SGSM3):c.58T>C(p.Trp20Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00961 in 1,613,356 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: 𝑓 0.0066 ( 7 hom., cov: 32)
Exomes 𝑓: 0.0099 ( 98 hom. )
Consequence
SGSM3
NM_015705.6 missense
NM_015705.6 missense
Scores
3
6
9
Clinical Significance
Conservation
PhyloP100: 5.45
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.005639255).
BP6
?
Variant 22-40401643-T-C is Benign according to our data. Variant chr22-40401643-T-C is described in ClinVar as [Benign]. Clinvar id is 782757.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAd at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SGSM3 | NM_015705.6 | c.58T>C | p.Trp20Arg | missense_variant | 3/22 | ENST00000248929.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGSM3 | ENST00000248929.14 | c.58T>C | p.Trp20Arg | missense_variant | 3/22 | 1 | NM_015705.6 | P1 | |
SGSM3 | ENST00000457767.5 | c.-111-496T>C | intron_variant | 2 | |||||
SGSM3 | ENST00000485962.5 | n.219T>C | non_coding_transcript_exon_variant | 3/20 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00656 AC: 998AN: 152216Hom.: 7 Cov.: 32
GnomAD3 genomes
?
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998
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GnomAD3 exomes AF: 0.00586 AC: 1473AN: 251474Hom.: 9 AF XY: 0.00600 AC XY: 815AN XY: 135906
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GnomAD4 exome AF: 0.00993 AC: 14506AN: 1461022Hom.: 98 Cov.: 31 AF XY: 0.00977 AC XY: 7099AN XY: 726822
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GnomAD4 genome ? AF: 0.00655 AC: 998AN: 152334Hom.: 7 Cov.: 32 AF XY: 0.00552 AC XY: 411AN XY: 74490
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ESP6500AA
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ESP6500EA
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99
ExAC
?
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686
Asia WGS
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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 submitter | clinical testing | Invitae | Feb 07, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Gain of disorder (P = 5e-04);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -50
Find out detailed SpliceAI scores and Pangolin per-transcript scores at