Genetic Variant PITX1:p.Gly7Asp (chr5-135033862-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002653.5(PITX1):c.20G>A(p.Gly7Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000113 in 1,329,174 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G7V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

PITX1
NM_002653.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.97

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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 15 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002653.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITX1	NM_002653.5	MANE Select	c.20G>A	p.Gly7Asp	missense	Exon 1 of 3	NP_002644.4
	PITX1-AS1	NR_161235.1		n.267+322C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PITX1	ENST00000265340.12	TSL:1 MANE Select	c.20G>A	p.Gly7Asp	missense	Exon 1 of 3	ENSP00000265340.6	P78337
PITX1	ENST00000506438.5	TSL:1	c.20G>A	p.Gly7Asp	missense	Exon 2 of 4	ENSP00000427542.1	P78337
PITX1	ENST00000507253.5	TSL:3	c.20G>A	p.Gly7Asp	missense	Exon 2 of 3	ENSP00000422908.1	D6R9U1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000241

AC:

AN:

82874

AF XY:

0.0000210

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000113

AC:

AN:

1329174

Hom.:

Cov.:

AF XY:

0.0000122

AC XY:

AN XY:

655782

show subpopulations

African (AFR)

AF:

0.0000377

AC:

AN:

26526

American (AMR)

AF:

0.00

AC:

AN:

26864

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22140

East Asian (EAS)

AF:

0.00

AC:

AN:

31140

South Asian (SAS)

AF:

0.0000692

AC:

AN:

72232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33828

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3844

European-Non Finnish (NFE)

AF:

0.00000851

AC:

AN:

1057558

Other (OTH)

AF:

0.00

AC:

AN:

55042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

Eigen

Benign

0.012

Eigen_PC

Benign

0.021

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.71

M_CAP

Pathogenic

0.95

MetaRNN

Uncertain

0.46

MetaSVM

Uncertain

0.16

MutationAssessor

Benign

1.8

PhyloP100

5.0

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.49

Sift

Benign

0.032

Sift4G

Benign

0.29

Polyphen

0.67

Vest4

0.43

MutPred

0.33

Loss of MoRF binding (P = 0.0125)

MVP

0.91

MPC

2.4

ClinPred

0.44

GERP RS

2.8

PromoterAI

0.042

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.20

gMVP

0.44

Mutation Taster

=84/16

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over