rs145233025

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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 š‘“: 0.0000027 ( 0 hom. )

Consequence

GCM1
NM_003643.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.290
Variant links:
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]

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ACMG classification

Classification made for transcript

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
GCM1NM_003643.4 linkc.1252T>C p.Tyr418His missense_variant Exon 6 of 6 ENST00000259803.8 NP_003634.2 Q9NP62

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GCM1ENST00000259803.8 linkc.1252T>C p.Tyr418His missense_variant Exon 6 of 6 1 NM_003643.4 ENSP00000259803.7 Q9NP62

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
show subpopulations
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
show subpopulations
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs145233025; hg19: chr6-52993063; API