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:

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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

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5-135033568-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