Genetic Variant PITX1:c.169+145C>T (chr5-135033568-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002653.5(PITX1):c.169+145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 845,952 control chromosomes in the GnomAD database, including 4,936 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.099 ( 814 hom., cov: 32)

Exomes 𝑓: 0.10 ( 4122 hom. )

Consequence

PITX1
NM_002653.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.578

Publications

0 publications found

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:

PITX1-AS1 (HGNC:48332): (PITX1 antisense RNA 1)

PITX1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 5-135033568-G-A is Benign according to our data. Variant chr5-135033568-G-A is described in ClinVar as [Benign]. Clinvar id is 1278728.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PITX1	NM_002653.5 link	c.169+145C>T	intron_variant	Intron 1 of 2	ENST00000265340.12	NP_002644.4	P78337X5D9A5
PITX1-AS1	NR_161235.1 link	n.267+28G>A	intron_variant	Intron 1 of 5
PITX1	XM_047417318.1 link	c.271+145C>T	intron_variant	Intron 2 of 3		XP_047273274.1
PITX1	XM_047417319.1 link	c.-307C>T	upstream_gene_variant			XP_047273275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITX1	ENST00000265340.12 link	c.169+145C>T		intron_variant	Intron 1 of 2	1	NM_002653.5	ENSP00000265340.6		P78337

Frequencies

GnomAD3 genomes

AF:

0.0984

AC:

14968

AN:

152160

Hom.:

804

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0803

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.0620

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.0478

Gnomad FIN

AF:

0.0754

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.106

GnomAD4 exome

AF:

0.102

AC:

70636

AN:

693674

Hom.:

4122

Cov.:

AF XY:

0.0992

AC XY:

35920

AN XY:

362000

show subpopulations

African (AFR)

AF:

0.0770

AC:

1163

AN:

15098

American (AMR)

AF:

0.168

AC:

4289

AN:

25510

Ashkenazi Jewish (ASJ)

AF:

0.0635

AC:

1120

AN:

17628

East Asian (EAS)

AF:

0.0000656

AC:

AN:

30496

South Asian (SAS)

AF:

0.0480

AC:

2821

AN:

58732

European-Finnish (FIN)

AF:

0.0803

AC:

2547

AN:

31712

Middle Eastern (MID)

AF:

0.0476

AC:

122

AN:

2564

European-Non Finnish (NFE)

AF:

0.116

AC:

55286

AN:

477698

Other (OTH)

AF:

0.0960

AC:

3286

AN:

34236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

3194

6388

9581

12775

15969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0985

AC:

15007

AN:

152278

Hom.:

814

Cov.:

AF XY:

0.0956

AC XY:

7118

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0803

AC:

3338

AN:

41574

American (AMR)

AF:

0.160

AC:

2446

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0620

AC:

215

AN:

3468

East Asian (EAS)

AF:

0.00175

AC:

AN:

5156

South Asian (SAS)

AF:

0.0489

AC:

236

AN:

4828

European-Finnish (FIN)

AF:

0.0754

AC:

800

AN:

10616

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.113

AC:

7704

AN:

68012

Other (OTH)

AF:

0.105

AC:

222

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

720

1441

2161

2882

3602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.100

Hom.:

110

Bravo

AF:

0.104

Asia WGS

AF:

0.0320

AC:

111

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 14, 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

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

0.58

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr5-135033568-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over