chr5-135028931-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002653.5(PITX1):ā€‹c.793G>Cā€‹(p.Gly265Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000855 in 1,613,850 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 34)
Exomes š‘“: 0.000092 ( 0 hom. )

Consequence

PITX1
NM_002653.5 missense

Scores

7
10
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.02
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 134 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PITX1NM_002653.5 linkc.793G>C p.Gly265Arg missense_variant Exon 3 of 3 ENST00000265340.12 NP_002644.4 P78337X5D9A5
PITX1XM_047417318.1 linkc.895G>C p.Gly299Arg missense_variant Exon 4 of 4 XP_047273274.1
PITX1XM_047417319.1 linkc.448G>C p.Gly150Arg missense_variant Exon 3 of 3 XP_047273275.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PITX1ENST00000265340.12 linkc.793G>C p.Gly265Arg missense_variant Exon 3 of 3 1 NM_002653.5 ENSP00000265340.6 P78337
PITX1ENST00000506438.5 linkc.793G>C p.Gly265Arg missense_variant Exon 4 of 4 1 ENSP00000427542.1 P78337

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152218
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000479
AC:
12
AN:
250326
Hom.:
0
AF XY:
0.0000664
AC XY:
9
AN XY:
135588
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000464
Gnomad NFE exome
AF:
0.0000973
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000917
AC:
134
AN:
1461632
Hom.:
0
Cov.:
34
AF XY:
0.0000853
AC XY:
62
AN XY:
727144
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:
0.0000375
Gnomad4 NFE exome
AF:
0.000119
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152218
Hom.:
0
Cov.:
34
AF XY:
0.0000134
AC XY:
1
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000847
Hom.:
0
Bravo
AF:
0.0000340
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.90
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.71
D;D
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
.;D
M_CAP
Pathogenic
0.68
D
MetaRNN
Uncertain
0.70
D;D
MetaSVM
Pathogenic
0.83
D
MutationAssessor
Uncertain
2.5
M;M
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-2.3
N;N
REVEL
Pathogenic
0.77
Sift
Uncertain
0.0070
D;D
Sift4G
Uncertain
0.0090
D;D
Polyphen
1.0
D;D
Vest4
0.23
MVP
0.95
MPC
2.3
ClinPred
0.36
T
GERP RS
4.1
Varity_R
0.47
gMVP
0.82

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: rs141612135; hg19: chr5-134364621; API