6-53134036-C-T

Position:

• chr6-53134036-C-T

Variant summary

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

The NM_003643.4(GCM1):​c.328+36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,596,416 control chromosomes in the GnomAD database, including 444,819 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.74 (42013 hom., cov: 32)
  • Exomes 𝑓: 0.75 (402806 hom.)
• Consequence: GCM1 NM_003643.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300

Genes affected

GCM1 (HGNC:4197): (glial cells missing transcription factor 1) This gene encodes a DNA-binding protein with a gcm-motif (glial cell missing motif). The encoded protein is a homolog of the Drosophila glial cells missing gene (gcm). This protein binds to the GCM-motif (A/G)CCCGCAT, a novel sequence among known targets of DNA-binding proteins. The N-terminal DNA-binding domain confers the unique DNA-binding activity of this protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCM1	NM_003643.4	c.328+36G>A		intron_variant		ENST00000259803.8	NP_003634.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCM1	ENST00000259803.8	c.328+36G>A		intron_variant		1	NM_003643.4	ENSP00000259803	P1

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112827 AN: 152066 Hom.: 41973 Cov.: 32

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.719

GnomAD3 exomes AF: 0.745 AC: 174202 AN: 233750 Hom.: 65306 AF XY: 0.744 AC XY: 94286 AN XY: 126656

Gnomad AFR exome AF: 0.724

Gnomad AMR exome AF: 0.803

Gnomad ASJ exome AF: 0.720

Gnomad EAS exome AF: 0.566

Gnomad SAS exome AF: 0.740

Gnomad FIN exome AF: 0.836

Gnomad NFE exome AF: 0.747

Gnomad OTH exome AF: 0.735

GnomAD4 exome AF: 0.745 AC: 1076585 AN: 1444232 Hom.: 402806 Cov.: 32 AF XY: 0.746 AC XY: 534586 AN XY: 716812

Gnomad4 AFR exome AF: 0.724

Gnomad4 AMR exome AF: 0.801

Gnomad4 ASJ exome AF: 0.723

Gnomad4 EAS exome AF: 0.542

Gnomad4 SAS exome AF: 0.743

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.748

Gnomad4 OTH exome AF: 0.735

GnomAD4 genome AF: 0.742 AC: 112924 AN: 152184 Hom.: 42013 Cov.: 32 AF XY: 0.746 AC XY: 55471 AN XY: 74392

Gnomad4 AFR AF: 0.723

Gnomad4 AMR AF: 0.777

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.845

Gnomad4 NFE AF: 0.747

Gnomad4 OTH AF: 0.720

Alfa AF: 0.737 Hom.: 8503

Bravo AF: 0.735

Asia WGS AF: 0.696 AC: 2422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs2816345; hg19: chr6-52998834; COSMIC: COSV52522295;