chr17-2375864-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014853.3(SGSM2):āc.2473G>Cā(p.Ala825Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000525 in 1,523,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000039 ( 0 hom., cov: 32)
Exomes š: 0.0000015 ( 0 hom. )
Consequence
SGSM2
NM_014853.3 missense
NM_014853.3 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 4.22
Genes affected
SGSM2 (HGNC:29026): (small G protein signaling modulator 2) The protein encoded by this gene is a GTPase activator with activity towards RAB32 and RAB33B, which are regulators of membrane trafficking. The encoded protein inactivates RAB32 and can bind RAB9A-GTP, a protein required for RAB32 activation. [provided by RefSeq, Oct 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18036401).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SGSM2 | NM_014853.3 | c.2473G>C | p.Ala825Pro | missense_variant | 18/24 | ENST00000268989.8 | NP_055668.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SGSM2 | ENST00000268989.8 | c.2473G>C | p.Ala825Pro | missense_variant | 18/24 | 1 | NM_014853.3 | ENSP00000268989 | P4 | |
SGSM2 | ENST00000426855.6 | c.2338G>C | p.Ala780Pro | missense_variant | 17/23 | 1 | ENSP00000415107 | A1 | ||
SGSM2-AS1 | ENST00000574290.1 | n.402-172C>G | intron_variant, non_coding_transcript_variant | 5 | ||||||
SGSM2 | ENST00000574563.5 | c.2338G>C | p.Ala780Pro | missense_variant | 17/23 | 2 | ENSP00000459126 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152212Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000279 AC: 5AN: 179082Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 94958
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GnomAD4 exome AF: 0.00000146 AC: 2AN: 1371132Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 674104
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152330Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74476
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 20, 2024 | The c.2473G>C (p.A825P) alteration is located in exon 18 (coding exon 18) of the SGSM2 gene. This alteration results from a G to C substitution at nucleotide position 2473, causing the alanine (A) at amino acid position 825 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;L
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.
REVEL
Benign
Sift
Benign
T;T;.
Sift4G
Benign
T;T;T
Polyphen
B;D;B
Vest4
MutPred
0.50
.;Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);
MVP
MPC
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at