NM_003643.4:c.75+174T>C

Variant names:

• chr6-53145384-A-G
• rs9367511
• NM_003643.4:c.75+174T>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.75+174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,088 control chromosomes in the GnomAD database, including 3,628 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 0.20 (3628 hom., cov: 31)
• Consequence: GCM1 NM_003643.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003643.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCM1	NM_003643.4	MANE Select	c.75+174T>C		intron	N/A	NP_003634.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCM1	ENST00000259803.8	TSL:1 MANE Select	c.75+174T>C		intron	N/A	ENSP00000259803.7	Q9NP62

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29830 AN: 151970 Hom.: 3608 Cov.: 31

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.189

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.197 AC: 29890 AN: 152088 Hom.: 3628 Cov.: 31 AF XY: 0.195 AC XY: 14514 AN XY: 74354

African (AFR) AF: 0.342 AC: 14147 AN: 41414

American (AMR) AF: 0.129 AC: 1977 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 657 AN: 3472

East Asian (EAS) AF: 0.263 AC: 1361 AN: 5170

South Asian (SAS) AF: 0.182 AC: 879 AN: 4822

European-Finnish (FIN) AF: 0.118 AC: 1251 AN: 10598

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8930 AN: 68002

Other (OTH) AF: 0.189 AC: 399 AN: 2116

Alfa AF: 0.157 Hom.: 6924

Bravo AF: 0.206

Asia WGS AF: 0.210 AC: 730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.36
PhyloP100		0.024
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: rs9367511; hg19: chr6-53010182;