5-135034150-CCCGGCTCCGGCT-CCCGGCTCCGGCTCCGGCT

Variant names:

• chr5-135034150-C-CCCGGCT
• rs372983845
• NM_002653.5:c.-275_-270dupAGCCGG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002653.5(PITX1):​c.-275_-270dupAGCCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: PITX1 NM_002653.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453

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 -4 ACMG points.

• BS2: High AC in GnomAd4 at 281 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITX1	NM_002653.5	c.-275_-270dupAGCCGG		5_prime_UTR_variant	Exon 1 of 3	ENST00000265340.12	NP_002644.4
PITX1	XM_047417318.1	c.35-207_35-202dupAGCCGG		intron_variant	Intron 1 of 3		XP_047273274.1
PITX1-AS1	NR_161235.1	n.267+630_267+635dupCGGCTC		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITX1	ENST00000265340.12	c.-275_-270dupAGCCGG		5_prime_UTR_variant	Exon 1 of 3	1	NM_002653.5	ENSP00000265340.6

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 281 AN: 149406 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00611

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000463

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.000204

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000195

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000313

Gnomad OTH AF: 0.000485

GnomAD4 exome AF: 0.00114 AC: 2 AN: 1760 Hom.: 0 Cov.: 0 AF XY: 0.00194 AC XY: 2 AN XY: 1032

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00163

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00188 AC: 281 AN: 149512 Hom.: 0 Cov.: 0 AF XY: 0.00175 AC XY: 128 AN XY: 72966

Gnomad4 AFR AF: 0.00609

Gnomad4 AMR AF: 0.000463

Gnomad4 ASJ AF: 0.000290

Gnomad4 EAS AF: 0.000204

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000195

Gnomad4 NFE AF: 0.000313

Gnomad4 OTH AF: 0.000480

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: rs372983845; hg19: chr5-134369840;