6-53131910-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003643.4(GCM1):​c.441+97G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 757,396 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000023 (0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS2: High AC in GnomAdExome4 at 14 AD gene.

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.441+97G>A		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.441+97G>A		intron	N/A	ENSP00000259803.7

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152026 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000231 AC: 14 AN: 605370 Hom.: 0 AF XY: 0.0000246 AC XY: 8 AN XY: 325764

African (AFR) AF: 0.00 AC: 0 AN: 17098

American (AMR) AF: 0.0000273 AC: 1 AN: 36636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19966

East Asian (EAS) AF: 0.00 AC: 0 AN: 34070

South Asian (SAS) AF: 0.0000156 AC: 1 AN: 64246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4100

European-Non Finnish (NFE) AF: 0.0000346 AC: 12 AN: 346934

Other (OTH) AF: 0.00 AC: 0 AN: 32084

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152026 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74246

African (AFR) AF: 0.00 AC: 0 AN: 41386

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 17

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.47
PhyloP100		-0.63

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;