chr1-108898962-T-G
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_013296.5(GPSM2):c.765T>G(p.Leu255Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000605 in 1,454,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000060 ( 0 hom. )
Consequence
GPSM2
NM_013296.5 synonymous
NM_013296.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.360
Publications
1 publications found
Genes affected
GPSM2 (HGNC:29501): (G protein signaling modulator 2) The protein encoded by this gene belongs to a family of proteins that modulate activation of G proteins, which transduce extracellular signals received by cell surface receptors into integrated cellular responses. The N-terminal half of this protein contains 10 copies of leu-gly-asn (LGN) repeat, and the C-terminal half contains 4 GoLoco motifs, which are involved in guanine nucleotide exchange. This protein may play a role in neuroblast division and in the development of normal hearing. Mutations in this gene are associated with autosomal recessive nonsyndromic deafness (DFNB82). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]
CLCC1 (HGNC:29675): (chloride channel CLIC like 1) Predicted to enable chloride channel activity. Predicted to be involved in chloride transport. Located in endoplasmic reticulum and mitochondria-associated endoplasmic reticulum membrane. Implicated in retinitis pigmentosa 32. [provided by Alliance of Genome Resources, Apr 2022]
AKNAD1 (HGNC:28398): (AKNA domain containing 1) This gene encodes a protein which contains a domain found in an AT-hook-containing transcription factor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 1-108898962-T-G is Benign according to our data. Variant chr1-108898962-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 505420.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.36 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_013296.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GPSM2 | NM_013296.5 | MANE Select | c.765T>G | p.Leu255Leu | synonymous | Exon 7 of 15 | NP_037428.3 | ||
| GPSM2 | NM_001321038.2 | c.765T>G | p.Leu255Leu | synonymous | Exon 7 of 15 | NP_001307967.1 | |||
| GPSM2 | NM_001321039.3 | c.765T>G | p.Leu255Leu | synonymous | Exon 7 of 16 | NP_001307968.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GPSM2 | ENST00000264126.9 | TSL:1 MANE Select | c.765T>G | p.Leu255Leu | synonymous | Exon 7 of 15 | ENSP00000264126.3 | ||
| GPSM2 | ENST00000674914.1 | c.816T>G | p.Leu272Leu | synonymous | Exon 8 of 16 | ENSP00000501579.1 | |||
| GPSM2 | ENST00000675087.1 | c.816T>G | p.Leu272Leu | synonymous | Exon 9 of 17 | ENSP00000502020.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.0000160 AC: 4AN: 250710 AF XY: 0.0000147 show subpopulations
GnomAD2 exomes
AF:
AC:
4
AN:
250710
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000605 AC: 88AN: 1454620Hom.: 0 Cov.: 28 AF XY: 0.0000497 AC XY: 36AN XY: 724114 show subpopulations
GnomAD4 exome
AF:
AC:
88
AN:
1454620
Hom.:
Cov.:
28
AF XY:
AC XY:
36
AN XY:
724114
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33296
American (AMR)
AF:
AC:
0
AN:
44712
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26098
East Asian (EAS)
AF:
AC:
0
AN:
39622
South Asian (SAS)
AF:
AC:
0
AN:
86096
European-Finnish (FIN)
AF:
AC:
0
AN:
53406
Middle Eastern (MID)
AF:
AC:
0
AN:
5690
European-Non Finnish (NFE)
AF:
AC:
86
AN:
1105594
Other (OTH)
AF:
AC:
1
AN:
60106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.469
Heterozygous variant carriers
0
4
9
13
18
22
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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10
20
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<30
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
ClinVar submissions as Germline
Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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