Variant 2-69844206-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_178439.5(GMCL1):c.758+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,478,404 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0078 ( 5 hom., cov: 32)

Exomes 𝑓: 0.010 ( 88 hom. )

Consequence

GMCL1
NM_178439.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.581

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 2-69844206-T-C is Benign according to our data. Variant chr2-69844206-T-C is described in ClinVar as [Benign]. Clinvar id is 771844.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GMCL1	NM_178439.5 linkuse as main transcript	c.758+10T>C		intron_variant		ENST00000282570.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GMCL1	ENST00000282570.4 linkuse as main transcript	c.758+10T>C		intron_variant		1	NM_178439.5	P1
GMCL1	ENST00000471404.1 linkuse as main transcript	n.628+10T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00779

AC:

1185

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00244

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00720

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00433

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0131

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00741

AC:

1656

AN:

223628

Hom.:

AF XY:

0.00749

AC XY:

914

AN XY:

121958

show subpopulations

Gnomad AFR exome

AF:

0.00254

Gnomad AMR exome

AF:

0.00824

Gnomad ASJ exome

AF:

0.00177

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000596

Gnomad FIN exome

AF:

0.00311

Gnomad NFE exome

AF:

0.0119

Gnomad OTH exome

AF:

0.00867

GnomAD4 exome

AF:

0.0103

AC:

13627

AN:

1326094

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

6660

AN XY:

664812

show subpopulations

Gnomad4 AFR exome

AF:

0.00191

Gnomad4 AMR exome

AF:

0.00746

Gnomad4 ASJ exome

AF:

0.00151

Gnomad4 EAS exome

AF:

0.0000264

Gnomad4 SAS exome

AF:

0.000549

Gnomad4 FIN exome

AF:

0.00402

Gnomad4 NFE exome

AF:

0.0124

Gnomad4 OTH exome

AF:

0.00835

GnomAD4 genome

AF:

0.00778

AC:

1185

AN:

152310

Hom.:

Cov.:

AF XY:

0.00717

AC XY:

534

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00243

Gnomad4 AMR

AF:

0.00719

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00433

Gnomad4 NFE

AF:

0.0131

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00897

Hom.:

Bravo

AF:

0.00791

Asia WGS

AF:

0.000873

AC:

AN:

3452

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

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.88

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