chr1-110060761-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006492.3(ALX3):c.1004C>T(p.Pro335Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000844 in 1,493,494 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000028 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000090 ( 0 hom. )
Consequence
ALX3
NM_006492.3 missense
NM_006492.3 missense
Scores
10
4
Clinical Significance
Conservation
PhyloP100: 2.18
Genes affected
ALX3 (HGNC:449): (ALX homeobox 3) This gene encodes a nuclear protein with a homeobox DNA-binding domain that functions as a transcriptional regulator involved in cell-type differentiation and development. Preferential methylation of this gene's promoter is associated with advanced-stage neuroblastoma tumors. [provided by RefSeq, Jul 2008]
STRIP1 (HGNC:25916): (striatin interacting protein 1) This gene encodes a member of the striatin-interacting phosphatase and kinase complex, which is involved in localization of the Golgi body. The encoded protein participates in cytosketelal organization. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALX3 | NM_006492.3 | c.1004C>T | p.Pro335Leu | missense_variant | 4/4 | ENST00000647563.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALX3 | ENST00000647563.2 | c.1004C>T | p.Pro335Leu | missense_variant | 4/4 | NM_006492.3 | P1 | ||
ENST00000554749.1 | n.2422G>A | non_coding_transcript_exon_variant | 1/1 | ||||||
ALX3 | ENST00000649954.1 | c.575C>T | p.Pro192Leu | missense_variant | 3/3 | ||||
STRIP1 | ENST00000473429.5 | n.4213+5959G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000279 AC: 4AN: 143602Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000284 AC: 7AN: 246584Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133400
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GnomAD4 exome AF: 0.0000904 AC: 122AN: 1349892Hom.: 0 Cov.: 35 AF XY: 0.0000947 AC XY: 63AN XY: 664968
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GnomAD4 genome ? AF: 0.0000279 AC: 4AN: 143602Hom.: 0 Cov.: 33 AF XY: 0.0000143 AC XY: 1AN XY: 69854
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 28, 2023 | The c.1004C>T (p.P335L) alteration is located in exon 4 (coding exon 4) of the ALX3 gene. This alteration results from a C to T substitution at nucleotide position 1004, causing the proline (P) at amino acid position 335 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Polyphen
D;D;.
Vest4
0.48
MVP
0.95
MPC
0.49
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at