NM_002653.5:c.*54C>A

Variant names:

• chr5-135028725-G-T
• rs1131614
• NM_002653.5:c.*54C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002653.5(PITX1):​c.*54C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PITX1 NM_002653.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• clubfoot

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• brachydactyly-elbow wrist dysplasia syndrome

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITX1	NM_002653.5	c.*54C>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000265340.12	NP_002644.4
PITX1	XM_047417318.1	c.*54C>A		3_prime_UTR_variant	Exon 4 of 4		XP_047273274.1
PITX1	XM_047417319.1	c.*54C>A		3_prime_UTR_variant	Exon 3 of 3		XP_047273275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITX1	ENST00000265340.12	c.*54C>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_002653.5	ENSP00000265340.6
PITX1	ENST00000506438.5	c.*54C>A		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000427542.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1130586 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 544836

African (AFR) AF: 0.00 AC: 0 AN: 22352

American (AMR) AF: 0.00 AC: 0 AN: 9710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14602

East Asian (EAS) AF: 0.00 AC: 0 AN: 26946

South Asian (SAS) AF: 0.00 AC: 0 AN: 39222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3118

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 940534

Other (OTH) AF: 0.00 AC: 0 AN: 45880

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 53

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.8
DANN	Benign	0.84
PhyloP100		-1.0

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

Other links and lift over

dbSNP: rs1131614; hg19: chr5-134364415;