chr2-69871767-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_178439.5(GMCL1):āc.1387A>Gā(p.Ser463Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000191 in 1,574,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
GMCL1
NM_178439.5 missense
NM_178439.5 missense
Scores
8
10
Clinical Significance
Conservation
PhyloP100: 3.64
Genes affected
GMCL1 (HGNC:23843): (germ cell-less 1, spermatogenesis associated) This gene encodes a nuclear envelope protein that appears to be involved in spermatogenesis, either directly or by influencing genes that play a more direct role in the process. This multi-exon locus is the homolog of the mouse and drosophila germ cell-less gene but the human genome also contains a single-exon locus on chromosome 5 that contains an open reading frame capable of encoding a highly-related protein. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26924717).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GMCL1 | NM_178439.5 | c.1387A>G | p.Ser463Gly | missense_variant | 13/14 | ENST00000282570.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GMCL1 | ENST00000282570.4 | c.1387A>G | p.Ser463Gly | missense_variant | 13/14 | 1 | NM_178439.5 | P1 | |
GMCL1 | ENST00000495047.1 | n.331A>G | non_coding_transcript_exon_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152048Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000842 AC: 2AN: 237528Hom.: 0 AF XY: 0.00000778 AC XY: 1AN XY: 128510
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GnomAD4 exome AF: 0.00000141 AC: 2AN: 1421964Hom.: 0 Cov.: 25 AF XY: 0.00000141 AC XY: 1AN XY: 707698
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152048Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74254
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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 | Mar 17, 2023 | The c.1387A>G (p.S463G) alteration is located in exon 13 (coding exon 13) of the GMCL1 gene. This alteration results from a A to G substitution at nucleotide position 1387, causing the serine (S) at amino acid position 463 to be replaced by a glycine (G). 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
Uncertain
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MutPred
Loss of phosphorylation at S463 (P = 0.073);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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