chr6-53128204-G-A

Variant names:

• chr6-53128204-G-A
• rs13200319
• NM_003643.4:c.*2C>T

Variant summary

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

The NM_003643.4(GCM1):​c.*2C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,598,990 control chromosomes in the GnomAD database, including 11,156 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 0.098 (842 hom., cov: 31)
  • Exomes 𝑓: 0.12 (10314 hom.)
• Consequence: GCM1 NM_003643.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCM1	NM_003643.4	c.*2C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000259803.8	NP_003634.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCM1	ENST00000259803	c.*2C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_003643.4	ENSP00000259803.7

Frequencies

GnomAD3 genomes AF: 0.0979 AC: 14879 AN: 151938 Hom.: 841 Cov.: 31

Gnomad AFR AF: 0.0508

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0962

Gnomad ASJ AF: 0.0882

Gnomad EAS AF: 0.0665

Gnomad SAS AF: 0.0477

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.107

GnomAD3 exomes AF: 0.0962 AC: 23306 AN: 242366 Hom.: 1220 AF XY: 0.0967 AC XY: 12712 AN XY: 131436

Gnomad AFR exome AF: 0.0526

Gnomad AMR exome AF: 0.0744

Gnomad ASJ exome AF: 0.0846

Gnomad EAS exome AF: 0.0722

Gnomad SAS exome AF: 0.0501

Gnomad FIN exome AF: 0.123

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.108

GnomAD4 exome AF: 0.116 AC: 168463 AN: 1446934 Hom.: 10314 Cov.: 32 AF XY: 0.115 AC XY: 82620 AN XY: 719662

Gnomad4 AFR exome AF: 0.0491

Gnomad4 AMR exome AF: 0.0725

Gnomad4 ASJ exome AF: 0.0889

Gnomad4 EAS exome AF: 0.0680

Gnomad4 SAS exome AF: 0.0506

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.0979 AC: 14883 AN: 152056 Hom.: 842 Cov.: 31 AF XY: 0.0969 AC XY: 7199 AN XY: 74316

Gnomad4 AFR AF: 0.0509

Gnomad4 AMR AF: 0.0960

Gnomad4 ASJ AF: 0.0882

Gnomad4 EAS AF: 0.0666

Gnomad4 SAS AF: 0.0477

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.106

Alfa AF: 0.112 Hom.: 410

Bravo AF: 0.0943

Asia WGS AF: 0.0590 AC: 203 AN: 3478

EpiCase AF: 0.124

EpiControl AF: 0.116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.20

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: rs13200319; hg19: chr6-52993002;