Variant 2-69830092-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178439.5(GMCL1):c.200A>G(p.Glu67Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000154 in 1,426,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

GMCL1
NM_178439.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.03

Variant links:

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]

GMCL1 links:

Genome browser will be placed here

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=0.15146163).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GMCL1	NM_178439.5 linkuse as main transcript	c.200A>G	p.Glu67Gly	missense_variant	1/14	ENST00000282570.4
GMCL1	XM_011533033.3 linkuse as main transcript	c.200A>G	p.Glu67Gly	missense_variant	1/13
GMCL1	XR_007079574.1 linkuse as main transcript	n.433A>G		non_coding_transcript_exon_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GMCL1	ENST00000282570.4 linkuse as main transcript	c.200A>G	p.Glu67Gly	missense_variant	1/14	1	NM_178439.5	P1
GMCL1	ENST00000468386.2 linkuse as main transcript	n.407A>G		non_coding_transcript_exon_variant	1/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000157

AC:

AN:

190866

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

102052

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000120

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000154

AC:

AN:

1426014

Hom.:

Cov.:

AF XY:

0.0000184

AC XY:

AN XY:

705714

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000508

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000250

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jan 30, 2024

The c.200A>G (p.E67G) alteration is located in exon 1 (coding exon 1) of the GMCL1 gene. This alteration results from a A to G substitution at nucleotide position 200, causing the glutamic acid (E) at amino acid position 67 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.051

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.73

M_CAP

Benign

0.049

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.7

REVEL

Benign

0.10

Sift

Benign

0.082

Sift4G

Uncertain

0.010

Polyphen

0.10

Vest4

0.21

MutPred

0.29

Loss of solvent accessibility (P = 0.0187);

MVP

0.70

MPC

0.48

ClinPred

0.38

GERP RS

4.6

Varity_R

0.14

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over