chr5-135034150-C-CCCGGCTCCGGCT

Variant names:

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

Variant summary

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

The NM_002653.5(PITX1):​c.-281_-270dupAGCCGGAGCCGG 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 INS_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 0.000054 (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: -0.453
• 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 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002653.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITX1	NM_002653.5	MANE Select	c.-281_-270dupAGCCGGAGCCGG		5_prime_UTR	Exon 1 of 3	NP_002644.4
	PITX1-AS1	NR_161235.1		n.267+624_267+635dupCGGCTCCGGCTC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITX1	ENST00000265340.12	TSL:1 MANE Select	c.-281_-270dupAGCCGGAGCCGG		5_prime_UTR	Exon 1 of 3	ENSP00000265340.6	P78337
	PITX1	ENST00000506438.5	TSL:1	c.-68-213_-68-202dupAGCCGGAGCCGG		intron	N/A	ENSP00000427542.1	P78337
	PITX1	ENST00000507253.5	TSL:3	c.-68-213_-68-202dupAGCCGGAGCCGG		intron	N/A	ENSP00000422908.1	D6R9U1

Frequencies

GnomAD3 genomes AF: 0.0000469 AC: 7 AN: 149406 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000815

Gnomad SAS AF: 0.000628

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1760 Hom.: 0 Cov.: 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: 0.0000535 AC: 8 AN: 149512 Hom.: 0 Cov.: 0 AF XY: 0.0000822 AC XY: 6 AN XY: 72966

African (AFR) AF: 0.00 AC: 0 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: 0.000817 AC: 4 AN: 4894

South Asian (SAS) AF: 0.000628 AC: 3 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: 0.00 AC: 0 AN: 67038

Other (OTH) AF: 0.000480 AC: 1 AN: 2084

Alfa AF: 0.00 Hom.: 272

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.45

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;