5-178186543-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001358008.2(GMCL2):c.757G>A(p.Gly253Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,300,708 control chromosomes in the GnomAD database, including 8,948 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/9 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1778 hom., cov: 33)
  • Exomes 𝑓: 0.11 (7170 hom.)
• Consequence: GMCL2 NM_001358008.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333

Genes affected

GMCL2 (HGNC:19717): (germ cell-less 2, spermatogenesis associated) This locus shares a high degree of identity with the multi-exon germ cell-less gene on chromosome 2. Despite its single-exon nature, this chromosome 5 locus contains an open reading frame that could putatively encode a full-length germ cell-less related protein. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033006966).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GMCL2	NM_001358008.2	c.757G>A	p.Gly253Ser	missense_variant	1/1	ENST00000463439.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GMCL2	ENST00000463439.3	c.757G>A	p.Gly253Ser	missense_variant	1/1		NM_001358008.2	P1
	ENST00000697324.1	n.328+3552C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20523 AN: 152038 Hom.: 1773 Cov.: 33

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0871

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.0179

Gnomad SAS AF: 0.0646

Gnomad FIN AF: 0.0969

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.108

GnomAD3 exomes AF: 0.0954 AC: 23978 AN: 251360 Hom.: 1462 AF XY: 0.0930 AC XY: 12634 AN XY: 135898

Gnomad AFR exome AF: 0.237

Gnomad AMR exome AF: 0.0651

Gnomad ASJ exome AF: 0.0621

Gnomad EAS exome AF: 0.00788

Gnomad SAS exome AF: 0.0710

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.0912

GnomAD4 exome AF: 0.106 AC: 121308 AN: 1148552 Hom.: 7170 Cov.: 20 AF XY: 0.104 AC XY: 60692 AN XY: 586212

Gnomad4 AFR exome AF: 0.247

Gnomad4 AMR exome AF: 0.0656

Gnomad4 ASJ exome AF: 0.0624

Gnomad4 EAS exome AF: 0.0420

Gnomad4 SAS exome AF: 0.0715

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.135 AC: 20548 AN: 152156 Hom.: 1778 Cov.: 33 AF XY: 0.132 AC XY: 9808 AN XY: 74398

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.0870

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.0179

Gnomad4 SAS AF: 0.0636

Gnomad4 FIN AF: 0.0969

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0943 Hom.: 442

Bravo AF: 0.137

TwinsUK AF: 0.100 AC: 371

ALSPAC AF: 0.110 AC: 423

ExAC AF: 0.101 AC: 12302

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.2
Dann	Benign	0.73
DEOGEN2	Benign	0.0088	T
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.14	T
MetaRNN	Benign	0.0033	T
Polyphen		0.0	B
GERP RS		-0.0076
Varity_R		0.043
gMVP		0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2961663; hg19: chr5-177613544;