rs1131614

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-135028725-G-A
• chr5-135028725-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002653.5(PITX1):​c.*54C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0678 in 1,281,232 control chromosomes in the GnomAD database, including 3,882 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.062 (443 hom., cov: 33)
  • Exomes 𝑓: 0.069 (3439 hom.)
• Consequence: PITX1 NM_002653.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-135028725-G-A is Benign according to our data. Variant chr5-135028725-G-A is described in ClinVar as [Benign]. Clinvar id is 1272199.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITX1	NM_002653.5	c.*54C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000265340.12	NP_002644.4
PITX1	XM_047417318.1	c.*54C>T		3_prime_UTR_variant	Exon 4 of 4		XP_047273274.1
PITX1	XM_047417319.1	c.*54C>T		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>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_002653.5	ENSP00000265340.6
PITX1	ENST00000506438.5	c.*54C>T		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000427542.1

Frequencies

GnomAD3 genomes AF: 0.0620 AC: 9358 AN: 150908 Hom.: 442 Cov.: 33

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0805

Gnomad ASJ AF: 0.0543

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.0912

Gnomad MID AF: 0.0258

Gnomad NFE AF: 0.0676

Gnomad OTH AF: 0.0487

GnomAD4 exome AF: 0.0685 AC: 77453 AN: 1130216 Hom.: 3439 Cov.: 20 AF XY: 0.0713 AC XY: 38812 AN XY: 544638

African (AFR) AF: 0.00962 AC: 215 AN: 22352

American (AMR) AF: 0.0907 AC: 880 AN: 9704

Ashkenazi Jewish (ASJ) AF: 0.0536 AC: 783 AN: 14600

East Asian (EAS) AF: 0.0886 AC: 2387 AN: 26942

South Asian (SAS) AF: 0.214 AC: 8365 AN: 39158

European-Finnish (FIN) AF: 0.0995 AC: 2808 AN: 28214

Middle Eastern (MID) AF: 0.0491 AC: 153 AN: 3116

European-Non Finnish (NFE) AF: 0.0623 AC: 58550 AN: 940266

Other (OTH) AF: 0.0722 AC: 3312 AN: 45864

GnomAD4 genome AF: 0.0620 AC: 9359 AN: 151016 Hom.: 443 Cov.: 33 AF XY: 0.0663 AC XY: 4891 AN XY: 73792

African (AFR) AF: 0.0141 AC: 581 AN: 41348

American (AMR) AF: 0.0806 AC: 1224 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.0543 AC: 188 AN: 3464

East Asian (EAS) AF: 0.135 AC: 689 AN: 5102

South Asian (SAS) AF: 0.187 AC: 899 AN: 4808

European-Finnish (FIN) AF: 0.0912 AC: 925 AN: 10146

Middle Eastern (MID) AF: 0.0174 AC: 5 AN: 288

European-Non Finnish (NFE) AF: 0.0676 AC: 4577 AN: 67664

Other (OTH) AF: 0.0525 AC: 110 AN: 2094

Alfa AF: 0.0676 Hom.: 53

Bravo AF: 0.0560

Asia WGS AF: 0.151 AC: 521 AN: 3450

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.7
DANN	Benign	0.94
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism

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;