rs145233025

Variant names:

• chr6-53128265-A-G
• rs145233025
• NM_003643.4:c.1252T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-53128265-A-G
• chr6-53128265-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003643.4(GCM1):​c.1252T>C​(p.Tyr418His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y418N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: GCM1 NM_003643.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.290

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1504857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCM1	NM_003643.4	c.1252T>C	p.Tyr418His	missense_variant	Exon 6 of 6	ENST00000259803.8	NP_003634.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCM1	ENST00000259803.8	c.1252T>C	p.Tyr418His	missense_variant	Exon 6 of 6	1	NM_003643.4	ENSP00000259803.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250902 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135622

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461098 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726894

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	6.7
DANN	Benign	0.69
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.20
Sift	Benign	0.080	T
Sift4G	Benign	0.53	T
Polyphen		0.91	P
Vest4		0.15
MutPred		0.44		Gain of disorder (P = 0.0144);
MVP		0.29
MPC		0.12
ClinPred		0.25	T
GERP RS		3.4
Varity_R		0.037
gMVP		0.15

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: rs145233025; hg19: chr6-52993063;