2-69869846-G-A
Position:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_178439.5(GMCL1):c.1346G>A(p.Arg449Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000906 in 1,613,536 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0045 ( 4 hom., cov: 29)
Exomes 𝑓: 0.00053 ( 5 hom. )
Consequence
GMCL1
NM_178439.5 missense
NM_178439.5 missense
Scores
1
2
14
Clinical Significance
Conservation
PhyloP100: 7.70
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.012802094).
BP6
Variant 2-69869846-G-A is Benign according to our data. Variant chr2-69869846-G-A is described in ClinVar as [Benign]. Clinvar id is 791856.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000532 (777/1461614) while in subpopulation AFR AF= 0.0193 (646/33466). AF 95% confidence interval is 0.0181. There are 5 homozygotes in gnomad4_exome. There are 353 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GMCL1 | NM_178439.5 | c.1346G>A | p.Arg449Gln | missense_variant | 12/14 | ENST00000282570.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GMCL1 | ENST00000282570.4 | c.1346G>A | p.Arg449Gln | missense_variant | 12/14 | 1 | NM_178439.5 | P1 | |
GMCL1 | ENST00000495047.1 | n.290G>A | non_coding_transcript_exon_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00450 AC: 683AN: 151804Hom.: 4 Cov.: 29
GnomAD3 genomes
AF:
AC:
683
AN:
151804
Hom.:
Cov.:
29
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00113 AC: 284AN: 251038Hom.: 1 AF XY: 0.000870 AC XY: 118AN XY: 135682
GnomAD3 exomes
AF:
AC:
284
AN:
251038
Hom.:
AF XY:
AC XY:
118
AN XY:
135682
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000532 AC: 777AN: 1461614Hom.: 5 Cov.: 31 AF XY: 0.000485 AC XY: 353AN XY: 727110
GnomAD4 exome
AF:
AC:
777
AN:
1461614
Hom.:
Cov.:
31
AF XY:
AC XY:
353
AN XY:
727110
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00451 AC: 685AN: 151922Hom.: 4 Cov.: 29 AF XY: 0.00455 AC XY: 338AN XY: 74250
GnomAD4 genome
AF:
AC:
685
AN:
151922
Hom.:
Cov.:
29
AF XY:
AC XY:
338
AN XY:
74250
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
70
ESP6500EA
AF:
AC:
2
ExAC
AF:
AC:
167
Asia WGS
AF:
AC:
4
AN:
3478
EpiCase
AF:
EpiControl
AF:
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 | May 04, 2018 | - - |
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
Pathogenic
D
LIST_S2
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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