12-85280452-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_006982.3(ALX1):ā€‹c.191G>Cā€‹(p.Arg64Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

ALX1
NM_006982.3 missense

Scores

3
8
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.82
Variant links:
Genes affected
ALX1 (HGNC:1494): (ALX homeobox 1) The specific function of this gene has yet to be determined in humans; however, in rodents, it is necessary for survival of the forebrain mesenchyme and may also be involved in development of the cervix. Mutations in the mouse gene lead to neural tube defects such as acrania and meroanencephaly. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.759

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ALX1NM_006982.3 linkuse as main transcriptc.191G>C p.Arg64Pro missense_variant 1/4 ENST00000316824.4 NP_008913.2 Q15699V9HWA7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ALX1ENST00000316824.4 linkuse as main transcriptc.191G>C p.Arg64Pro missense_variant 1/41 NM_006982.3 ENSP00000315417.3 Q15699

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1459630
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
726108
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Pathogenic
0.42
D
BayesDel_noAF
Pathogenic
0.36
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.049
T
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.062
D
MetaRNN
Pathogenic
0.76
D
MetaSVM
Uncertain
0.52
D
MutationAssessor
Benign
1.2
L
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-0.30
N
REVEL
Uncertain
0.58
Sift
Uncertain
0.016
D
Sift4G
Benign
0.21
T
Polyphen
0.99
D
Vest4
0.68
MutPred
0.49
Gain of catalytic residue at L65 (P = 0.012);
MVP
0.95
MPC
0.54
ClinPred
0.94
D
GERP RS
5.5
Varity_R
0.38
gMVP
0.53

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: rs115596276; hg19: chr12-85674230; COSMIC: COSV57493409; API