Genetic Variant PITX1:c.169+145C>G (chr5-135033568-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002653.5(PITX1):c.169+145C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000864 in 694,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

PITX1
NM_002653.5 intron

Scores

Clinical Significance

Not reported in ClinVar

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PITX1	NM_002653.5 link	c.169+145C>G	intron_variant	Intron 1 of 2	ENST00000265340.12	NP_002644.4	P78337X5D9A5
PITX1-AS1	NR_161235.1 link	n.267+28G>C	intron_variant	Intron 1 of 5
PITX1	XM_047417318.1 link	c.271+145C>G	intron_variant	Intron 2 of 3		XP_047273274.1
PITX1	XM_047417319.1 link	c.-307C>G	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>G		intron_variant	Intron 1 of 2	1	NM_002653.5	ENSP00000265340.6		P78337

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000864

AC:

AN:

694272

Hom.:

Cov.:

AF XY:

0.00000828

AC XY:

AN XY:

362330

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15120

American (AMR)

AF:

0.00

AC:

AN:

25538

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17630

East Asian (EAS)

AF:

0.00

AC:

AN:

30496

South Asian (SAS)

AF:

0.00

AC:

AN:

58750

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31720

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2564

European-Non Finnish (NFE)

AF:

0.0000125

AC:

AN:

478198

Other (OTH)

AF:

0.00

AC:

AN:

34256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr5-135033568-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over