5-135028810-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002653.5(PITX1):c.914C>T(p.Ser305Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,200 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
PITX1
NM_002653.5 missense
NM_002653.5 missense
Scores
2
13
4
Clinical Significance
Conservation
PhyloP100: 7.79
Genes affected
PITX1 (HGNC:9004): (paired like homeodomain 1) This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. Members of this family are involved in organ development and left-right asymmetry. This protein acts as a transcriptional regulator involved in basal and hormone-regulated activity of prolactin. [provided by RefSeq, Jul 2008]
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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 | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PITX1 | NM_002653.5 | c.914C>T | p.Ser305Leu | missense_variant | 3/3 | ENST00000265340.12 | NP_002644.4 | |
| PITX1 | XM_047417318.1 | c.1016C>T | p.Ser339Leu | missense_variant | 4/4 | XP_047273274.1 | ||
| PITX1 | XM_047417319.1 | c.569C>T | p.Ser190Leu | missense_variant | 3/3 | XP_047273275.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1458200Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 725330
GnomAD4 exome
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2
AN:
1458200
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
725330
Gnomad4 AFR exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 28, 2023 | The c.914C>T (p.S305L) alteration is located in exon 3 (coding exon 3) of the PITX1 gene. This alteration results from a C to T substitution at nucleotide position 914, causing the serine (S) at amino acid position 305 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
D
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;P
Vest4
MutPred
Loss of glycosylation at S305 (P = 0.0047);Loss of glycosylation at S305 (P = 0.0047);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.