chr5-135028924-GGAGTGCCGTACGGGCAAGCGCCCGGCGACATGGCC-G

Position:

• chr5-135028924-GGAGTGCCGTACGGGCAAGCGCCCGGCGACATGGCC-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_002653.5(PITX1):​c.765_799del​(p.Ala256ArgfsTer304) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 34)
• Consequence: PITX1 NM_002653.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.79

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.19 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-135028924-GGAGTGCCGTACGGGCAAGCGCCCGGCGACATGGCC-G is Pathogenic according to our data. Variant chr5-135028924-GGAGTGCCGTACGGGCAAGCGCCCGGCGACATGGCC-G is described in ClinVar as [Pathogenic]. Clinvar id is 37253.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PITX1	NM_002653.5	c.765_799del	p.Ala256ArgfsTer304	frameshift_variant	3/3	ENST00000265340.12
PITX1	XM_047417318.1	c.867_901del	p.Ala290ArgfsTer304	frameshift_variant	4/4
PITX1	XM_047417319.1	c.420_454del	p.Ala141ArgfsTer304	frameshift_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PITX1	ENST00000265340.12	c.765_799del	p.Ala256ArgfsTer304	frameshift_variant	3/3	1	NM_002653.5	P1
PITX1	ENST00000506438.5	c.765_799del	p.Ala256ArgfsTer?	frameshift_variant	4/4	1		P1

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Clubfoot Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 2012

- -

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: rs730882191; hg19: chr5-134364614;