chr5-135033813-TGGCGGC-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4BS2

The NM_002653.5(PITX1):​c.63_68delGCCGCC​(p.Pro22_Pro23del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000328 in 1,553,658 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: 𝑓 0.000046 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

PITX1
NM_002653.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.71
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]
PITX1-AS1 (HGNC:48332): (PITX1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM4
Nonframeshift variant in NON repetitive region in NM_002653.5.
BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PITX1NM_002653.5 linkc.63_68delGCCGCC p.Pro22_Pro23del disruptive_inframe_deletion Exon 1 of 3 ENST00000265340.12 NP_002644.4 P78337X5D9A5
PITX1XM_047417318.1 linkc.165_170delGCCGCC p.Pro56_Pro57del disruptive_inframe_deletion Exon 2 of 4 XP_047273274.1
PITX1-AS1NR_161235.1 linkn.267+283_267+288delGGCGGC intron_variant Intron 1 of 5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PITX1ENST00000265340.12 linkc.63_68delGCCGCC p.Pro22_Pro23del disruptive_inframe_deletion Exon 1 of 3 1 NM_002653.5 ENSP00000265340.6 P78337

Frequencies

GnomAD3 genomes
AF:
0.0000463
AC:
7
AN:
151168
Hom.:
0
Cov.:
31
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:
0.000196
Gnomad SAS
AF:
0.000625
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000444
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000316
AC:
5
AN:
158042
Hom.:
0
AF XY:
0.0000335
AC XY:
3
AN XY:
89438
show subpopulations
Gnomad AFR exome
AF:
0.000177
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000126
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000142
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000314
AC:
44
AN:
1402382
Hom.:
0
AF XY:
0.0000374
AC XY:
26
AN XY:
695838
show subpopulations
Gnomad4 AFR exome
AF:
0.0000340
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000281
Gnomad4 SAS exome
AF:
0.000111
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000275
Gnomad4 OTH exome
AF:
0.0000516
GnomAD4 genome
AF:
0.0000463
AC:
7
AN:
151276
Hom.:
0
Cov.:
31
AF XY:
0.0000812
AC XY:
6
AN XY:
73880
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000196
Gnomad4 SAS
AF:
0.000626
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000444
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs752690307; hg19: chr5-134369503; API