5-135034150-CCCGGCTCCGGCTCCGGCT-CCCGGCT

Variant names:

• chr5-135034150-CCCGGCTCCGGCT-C
• rs372983845
• NM_002653.5:c.-281_-270delAGCCGGAGCCGG

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002653.5(PITX1):​c.-281_-270delAGCCGGAGCCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PITX1 NM_002653.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.780
• Publications: 0 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-AS1 (HGNC:48332): (PITX1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITX1	NM_002653.5	c.-281_-270delAGCCGGAGCCGG		5_prime_UTR_variant	Exon 1 of 3	ENST00000265340.12	NP_002644.4
PITX1-AS1	NR_161235.1	n.267+624_267+635delCGGCTCCGGCTC		intron_variant	Intron 1 of 5
PITX1	XM_047417318.1	c.35-213_35-202delAGCCGGAGCCGG		intron_variant	Intron 1 of 3		XP_047273274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITX1	ENST00000265340.12	c.-281_-270delAGCCGGAGCCGG		5_prime_UTR_variant	Exon 1 of 3	1	NM_002653.5	ENSP00000265340.6

Frequencies

GnomAD3 genomes AF: 0.000127 AC: 19 AN: 149406 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000443

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: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1760 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 1032

African (AFR) AF: 0.00 AC: 0 AN: 26

American (AMR) AF: 0.00 AC: 0 AN: 42

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 48

East Asian (EAS) AF: 0.00 AC: 0 AN: 52

South Asian (SAS) AF: 0.00 AC: 0 AN: 46

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 10

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1230

Other (OTH) AF: 0.00 AC: 0 AN: 94

GnomAD4 genome AF: 0.000120 AC: 18 AN: 149512 Hom.: 0 Cov.: 0 AF XY: 0.0000685 AC XY: 5 AN XY: 72966

African (AFR) AF: 0.000417 AC: 17 AN: 40724

American (AMR) AF: 0.00 AC: 0 AN: 15128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 4894

South Asian (SAS) AF: 0.00 AC: 0 AN: 4776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67038

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 272

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.78

Splicing

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

Other links and lift over

dbSNP: rs372983845; hg19: chr5-134369840;