dbSNP rs1561470713: PITX1:p.Met237Ile (chr5-135029013-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002653.5(PITX1):c.711G>T(p.Met237Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PITX1
NM_002653.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.72

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITX1	NM_002653.5 link	c.711G>T	p.Met237Ile	missense_variant	Exon 3 of 3	ENST00000265340.12	NP_002644.4	P78337X5D9A5
PITX1	XM_047417318.1 link	c.813G>T	p.Met271Ile	missense_variant	Exon 4 of 4		XP_047273274.1
PITX1	XM_047417319.1 link	c.366G>T	p.Met122Ile	missense_variant	Exon 3 of 3		XP_047273275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PITX1	ENST00000265340.12 link	c.711G>T	p.Met237Ile	missense_variant	Exon 3 of 3	1	NM_002653.5	ENSP00000265340.6	P78337
PITX1	ENST00000506438.5 link	c.711G>T	p.Met237Ile	missense_variant	Exon 4 of 4	1		ENSP00000427542.1	P78337
PITX1	ENST00000503586.1 link	n.*209G>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Uncertain

0.094

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

T;T

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

.;D

M_CAP

Uncertain

0.29

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Uncertain

0.51

MutationAssessor

Benign

1.7

L;L

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.15

N;N

REVEL

Uncertain

0.45

Sift

Uncertain

0.019

D;D

Sift4G

Benign

0.11

T;T

Polyphen

0.53

P;P

Vest4

0.54

MutPred

0.21

Gain of catalytic residue at L242 (P = 0.1769);Gain of catalytic residue at L242 (P = 0.1769);

MVP

0.87

MPC

1.1

ClinPred

0.86

GERP RS

4.3

Varity_R

0.52

gMVP

0.33

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over