5-135028725-G-A

Position:

• chr5-135028725-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PITX1	NM_002653.5	c.*54C>T		3_prime_UTR_variant	3/3	ENST00000265340.12
PITX1	XM_047417318.1	c.*54C>T		3_prime_UTR_variant	4/4
PITX1	XM_047417319.1	c.*54C>T		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PITX1	ENST00000265340.12	c.*54C>T		3_prime_UTR_variant	3/3	1	NM_002653.5	P1
PITX1	ENST00000506438.5	c.*54C>T		3_prime_UTR_variant	4/4	1		P1

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

Gnomad4 AFR exome AF: 0.00962

Gnomad4 AMR exome AF: 0.0907

Gnomad4 ASJ exome AF: 0.0536

Gnomad4 EAS exome AF: 0.0886

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.0995

Gnomad4 NFE exome AF: 0.0623

Gnomad4 OTH exome AF: 0.0722

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

Gnomad4 AFR AF: 0.0141

Gnomad4 AMR AF: 0.0806

Gnomad4 ASJ AF: 0.0543

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.0912

Gnomad4 NFE AF: 0.0676

Gnomad4 OTH AF: 0.0525

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.7
DANN	Benign	0.94

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

Publications

LitVar

Other links and lift over

dbSNP: rs1131614; hg19: chr5-134364415;