5-135028716-TCCGCGC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002653.5(PITX1):c.*57_*62del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,245,734 control chromosomes in the GnomAD database, including 110,322 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (20166 hom., cov: 0)
  • Exomes 𝑓: 0.40 (90156 hom.)
• Consequence: PITX1 NM_002653.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.58

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 -10 ACMG points.

• BP6: Variant 5-135028716-TCCGCGC-T is Benign according to our data. Variant chr5-135028716-TCCGCGC-T is described in ClinVar as [Benign]. Clinvar id is 1261620.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PITX1	NM_002653.5	c.*57_*62del		3_prime_UTR_variant	3/3	ENST00000265340.12
PITX1	XM_047417318.1	c.*57_*62del		3_prime_UTR_variant	4/4
PITX1	XM_047417319.1	c.*57_*62del		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PITX1	ENST00000265340.12	c.*57_*62del		3_prime_UTR_variant	3/3	1	NM_002653.5	P1
PITX1	ENST00000506438.5	c.*57_*62del		3_prime_UTR_variant	4/4	1		P1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 73237 AN: 149584 Hom.: 20101 Cov.: 0

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.284

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.400 AC: 438506 AN: 1096048 Hom.: 90156 AF XY: 0.402 AC XY: 212107 AN XY: 527978

Gnomad4 AFR exome AF: 0.761

Gnomad4 AMR exome AF: 0.560

Gnomad4 ASJ exome AF: 0.327

Gnomad4 EAS exome AF: 0.583

Gnomad4 SAS exome AF: 0.495

Gnomad4 FIN exome AF: 0.363

Gnomad4 NFE exome AF: 0.382

Gnomad4 OTH exome AF: 0.424

GnomAD4 genome AF: 0.490 AC: 73366 AN: 149686 Hom.: 20166 Cov.: 0 AF XY: 0.485 AC XY: 35426 AN XY: 73046

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.458

Alfa AF: 0.246 Hom.: 524

Bravo AF: 0.512

Asia WGS AF: 0.515 AC: 1769 AN: 3442

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 14, 2021

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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: rs71660434; hg19: chr5-134364406;