6-53131910-C-G

Variant names:

• chr6-53131910-C-G
• rs9349655
• NM_003643.4:c.441+97G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003643.4(GCM1):​c.441+97G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0962 in 757,264 control chromosomes in the GnomAD database, including 4,743 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 0.085 (693 hom., cov: 32)
  • Exomes 𝑓: 0.099 (4050 hom.)
• Consequence: GCM1 NM_003643.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.628
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCM1	NM_003643.4	c.441+97G>C		intron_variant	Intron 4 of 5	ENST00000259803.8	NP_003634.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCM1	ENST00000259803.8	c.441+97G>C		intron_variant	Intron 4 of 5	1	NM_003643.4	ENSP00000259803.7

Frequencies

GnomAD3 genomes AF: 0.0855 AC: 12992 AN: 152002 Hom.: 692 Cov.: 32

Gnomad AFR AF: 0.0740

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.0695

Gnomad ASJ AF: 0.0869

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0533

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0792

Gnomad OTH AF: 0.0903

GnomAD4 exome AF: 0.0989 AC: 59837 AN: 605144 Hom.: 4050 AF XY: 0.101 AC XY: 32820 AN XY: 325654

African (AFR) AF: 0.0733 AC: 1252 AN: 17092

American (AMR) AF: 0.0759 AC: 2780 AN: 36624

Ashkenazi Jewish (ASJ) AF: 0.0819 AC: 1634 AN: 19960

East Asian (EAS) AF: 0.315 AC: 10728 AN: 34050

South Asian (SAS) AF: 0.144 AC: 9217 AN: 64228

European-Finnish (FIN) AF: 0.0571 AC: 2868 AN: 50224

Middle Eastern (MID) AF: 0.0807 AC: 331 AN: 4100

European-Non Finnish (NFE) AF: 0.0806 AC: 27949 AN: 346790

Other (OTH) AF: 0.0960 AC: 3078 AN: 32076

GnomAD4 genome AF: 0.0854 AC: 12993 AN: 152120 Hom.: 693 Cov.: 32 AF XY: 0.0866 AC XY: 6436 AN XY: 74360

African (AFR) AF: 0.0740 AC: 3069 AN: 41498

American (AMR) AF: 0.0695 AC: 1061 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0869 AC: 301 AN: 3464

East Asian (EAS) AF: 0.279 AC: 1440 AN: 5168

South Asian (SAS) AF: 0.158 AC: 758 AN: 4808

European-Finnish (FIN) AF: 0.0533 AC: 565 AN: 10598

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0792 AC: 5385 AN: 67988

Other (OTH) AF: 0.0908 AC: 192 AN: 2114

Alfa AF: 0.0306 Hom.: 17

Bravo AF: 0.0869

Asia WGS AF: 0.185 AC: 642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.59
DANN	Benign	0.37
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9349655; hg19: chr6-52996708; COSMIC: COSV52524537;