chr5-135028716-T-TCCGCGC

Variant names:

• chr5-135028716-T-TCCGCGC
• rs71660434
• NM_002653.5:c.*57_*62dupGCGCGG

Variant summary

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

The NM_002653.5(PITX1):​c.*57_*62dupGCGCGG variant causes a 3 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 0.000073 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000063 (0 hom.)
• Consequence: PITX1 NM_002653.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.756
• Publications: 2 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 -4 ACMG points.

• BS2: High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITX1	NM_002653.5	c.*57_*62dupGCGCGG		3_prime_UTR_variant	Exon 3 of 3	ENST00000265340.12	NP_002644.4
PITX1	XM_047417318.1	c.*57_*62dupGCGCGG		3_prime_UTR_variant	Exon 4 of 4		XP_047273274.1
PITX1	XM_047417319.1	c.*57_*62dupGCGCGG		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.*57_*62dupGCGCGG		3_prime_UTR_variant	Exon 3 of 3	1	NM_002653.5	ENSP00000265340.6
PITX1	ENST00000506438.5	c.*57_*62dupGCGCGG		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000427542.1

Frequencies

GnomAD3 genomes AF: 0.0000735 AC: 11 AN: 149724 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000397

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000104

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000628 AC: 69 AN: 1098046 Hom.: 0 Cov.: 0 AF XY: 0.0000605 AC XY: 32 AN XY: 528894

African (AFR) AF: 0.00 AC: 0 AN: 21904

American (AMR) AF: 0.00 AC: 0 AN: 9154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13892

East Asian (EAS) AF: 0.000573 AC: 15 AN: 26156

South Asian (SAS) AF: 0.0000273 AC: 1 AN: 36574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3002

European-Non Finnish (NFE) AF: 0.0000524 AC: 48 AN: 916154

Other (OTH) AF: 0.000112 AC: 5 AN: 44608

GnomAD4 genome AF: 0.0000734 AC: 11 AN: 149826 Hom.: 0 Cov.: 0 AF XY: 0.0000821 AC XY: 6 AN XY: 73126

African (AFR) AF: 0.00 AC: 0 AN: 40906

American (AMR) AF: 0.0000662 AC: 1 AN: 15106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.000399 AC: 2 AN: 5018

South Asian (SAS) AF: 0.000210 AC: 1 AN: 4766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9980

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

European-Non Finnish (NFE) AF: 0.000104 AC: 7 AN: 67338

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 524

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.76
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs71660434; hg19: chr5-134364406;