6-53134058-T-G

Position:

• chr6-53134058-T-G

Variant summary

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

The NM_003643.4(GCM1):​c.328+14A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 1,608,394 control chromosomes in the GnomAD database, including 423,696 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 0.68 (36061 hom., cov: 32)
  • Exomes 𝑓: 0.73 (387635 hom.)
• Consequence: GCM1 NM_003643.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCM1	NM_003643.4	c.328+14A>C		intron_variant		ENST00000259803.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCM1	ENST00000259803.8	c.328+14A>C		intron_variant		1	NM_003643.4	P1

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103814 AN: 151994 Hom.: 36028 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.662

GnomAD3 exomes AF: 0.721 AC: 178044 AN: 246840 Hom.: 64940 AF XY: 0.724 AC XY: 96606 AN XY: 133486

Gnomad AFR exome AF: 0.549

Gnomad AMR exome AF: 0.786

Gnomad ASJ exome AF: 0.666

Gnomad EAS exome AF: 0.568

Gnomad SAS exome AF: 0.734

Gnomad FIN exome AF: 0.827

Gnomad NFE exome AF: 0.733

Gnomad OTH exome AF: 0.715

GnomAD4 exome AF: 0.728 AC: 1059730 AN: 1456282 Hom.: 387635 Cov.: 41 AF XY: 0.729 AC XY: 527148 AN XY: 723514

Gnomad4 AFR exome AF: 0.551

Gnomad4 AMR exome AF: 0.781

Gnomad4 ASJ exome AF: 0.668

Gnomad4 EAS exome AF: 0.542

Gnomad4 SAS exome AF: 0.736

Gnomad4 FIN exome AF: 0.824

Gnomad4 NFE exome AF: 0.735

Gnomad4 OTH exome AF: 0.710

GnomAD4 genome AF: 0.683 AC: 103897 AN: 152112 Hom.: 36061 Cov.: 32 AF XY: 0.688 AC XY: 51178 AN XY: 74374

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.658

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.715

Gnomad4 FIN AF: 0.835

Gnomad4 NFE AF: 0.734

Gnomad4 OTH AF: 0.664

Alfa AF: 0.658 Hom.: 4831

Bravo AF: 0.669

Asia WGS AF: 0.684 AC: 2380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2518573; hg19: chr6-52998856; COSMIC: COSV52522307;