Variant 5-135029401-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002653.5(PITX1):c.403-80A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,218,474 control chromosomes in the GnomAD database, including 105,779 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.49 ( 20641 hom., cov: 33)

Exomes 𝑓: 0.39 ( 85138 hom. )

Consequence

PITX1
NM_002653.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.13

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 5-135029401-T-C is Benign according to our data. Variant chr5-135029401-T-C is described in ClinVar as [Benign]. Clinvar id is 1294906.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
PITX1	NM_002653.5 link	c.403-80A>G	intron_variant	ENST00000265340.12	NP_002644.4	P78337X5D9A5
PITX1	XM_047417318.1 link	c.505-80A>G	intron_variant		XP_047273274.1
PITX1	XM_047417319.1 link	c.58-80A>G	intron_variant		XP_047273275.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
PITX1	ENST00000265340.12 link	c.403-80A>G	intron_variant	1	NM_002653.5	ENSP00000265340.6	P78337
PITX1	ENST00000506438.5 link	c.403-80A>G	intron_variant	1		ENSP00000427542.1	P78337
PITX1	ENST00000503586.1 link	n.525-80A>G	intron_variant	3
PITX1	ENST00000504936.1 link	n.736-80A>G	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.491

AC:

74638

AN:

152036

Hom.:

20575

Cov.:

show subpopulations

Gnomad AFR

AF:

0.747

Gnomad AMI

AF:

0.383

Gnomad AMR

AF:

0.507

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.466

Gnomad FIN

AF:

0.326

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.373

Gnomad OTH

AF:

0.455

GnomAD4 exome

AF:

0.391

AC:

416471

AN:

1066322

Hom.:

85138

AF XY:

0.391

AC XY:

208347

AN XY:

532916

show subpopulations

Gnomad4 AFR exome

AF:

0.746

Gnomad4 AMR exome

AF:

0.538

Gnomad4 ASJ exome

AF:

0.310

Gnomad4 EAS exome

AF:

0.546

Gnomad4 SAS exome

AF:

0.437

Gnomad4 FIN exome

AF:

0.338

Gnomad4 NFE exome

AF:

0.368

Gnomad4 OTH exome

AF:

0.404

GnomAD4 genome

AF:

0.491

AC:

74772

AN:

152152

Hom.:

20641

Cov.:

AF XY:

0.486

AC XY:

36182

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.748

Gnomad4 AMR

AF:

0.508

Gnomad4 ASJ

AF:

0.302

Gnomad4 EAS

AF:

0.473

Gnomad4 SAS

AF:

0.466

Gnomad4 FIN

AF:

0.326

Gnomad4 NFE

AF:

0.373

Gnomad4 OTH

AF:

0.457

Alfa

AF:

0.394

Hom.:

15615

Bravo

AF:

0.515

Asia WGS

AF:

0.524

AC:

1820

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.5

DANN

Benign

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over