5-135033813-TGGCGGC-TGGCGGCGGCGGC

Variant names:

• chr5-135033813-T-TGGCGGC
• rs752690307
• NM_002653.5:c.63_68dupGCCGCC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4 BS2

The NM_002653.5(PITX1):​c.63_68dupGCCGCC​(p.Pro22_Pro23dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0000187 in 1,553,548 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 0.000033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: PITX1 NM_002653.5 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.71

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)

ACMG classification

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 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITX1	NM_002653.5	c.63_68dupGCCGCC	p.Pro22_Pro23dup	disruptive_inframe_insertion	Exon 1 of 3	ENST00000265340.12	NP_002644.4
PITX1	XM_047417318.1	c.165_170dupGCCGCC	p.Pro56_Pro57dup	disruptive_inframe_insertion	Exon 2 of 4		XP_047273274.1
PITX1-AS1	NR_161235.1	n.267+283_267+288dupGGCGGC		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITX1	ENST00000265340.12	c.63_68dupGCCGCC	p.Pro22_Pro23dup	disruptive_inframe_insertion	Exon 1 of 3	1	NM_002653.5	ENSP00000265340.6

Frequencies

GnomAD3 genomes AF: 0.0000331 AC: 5 AN: 151168 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000486

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: 0.0000444

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000127 AC: 2 AN: 158042 Hom.: 0 AF XY: 0.0000112 AC XY: 1 AN XY: 89438

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000142

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 24 AN: 1402380 Hom.: 0 Cov.: 31 AF XY: 0.0000216 AC XY: 15 AN XY: 695836

Gnomad4 AFR exome AF: 0.000204

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000123

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000147

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome AF: 0.0000331 AC: 5 AN: 151168 Hom.: 0 Cov.: 31 AF XY: 0.0000407 AC XY: 3 AN XY: 73764

Gnomad4 AFR AF: 0.0000486

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: 0.0000444

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs752690307; hg19: chr5-134369503;