5-135028828-C-G

Position:

chr5-135028828-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002653.5(PITX1):c.896G>C(p.Gly299Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,611,896 control chromosomes in the GnomAD database, including 61,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5044 hom., cov: 33)

Exomes 𝑓: 0.27 ( 56215 hom. )

Consequence

PITX1
NM_002653.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 7.54

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00277856).

BP6

Variant 5-135028828-C-G is Benign according to our data. Variant chr5-135028828-C-G is described in ClinVar as [Benign]. Clinvar id is 286868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-135028828-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PITX1	NM_002653.5 linkuse as main transcript	c.896G>C	p.Gly299Ala	missense_variant	3/3	ENST00000265340.12
PITX1	XM_047417318.1 linkuse as main transcript	c.998G>C	p.Gly333Ala	missense_variant	4/4
PITX1	XM_047417319.1 linkuse as main transcript	c.551G>C	p.Gly184Ala	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PITX1	ENST00000265340.12 linkuse as main transcript	c.896G>C	p.Gly299Ala	missense_variant	3/3	1	NM_002653.5	P1
PITX1	ENST00000506438.5 linkuse as main transcript	c.896G>C	p.Gly299Ala	missense_variant	4/4	1		P1

Frequencies

GnomAD3 genomes

AF:

0.244

AC:

36998

AN:

151880

Hom.:

5044

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.414

Gnomad FIN

AF:

0.251

Gnomad MID

AF:

0.201

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.229

GnomAD3 exomes

AF:

0.292

AC:

71893

AN:

246276

Hom.:

11240

AF XY:

0.295

AC XY:

39475

AN XY:

133960

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.345

Gnomad ASJ exome

AF:

0.247

Gnomad EAS exome

AF:

0.467

Gnomad SAS exome

AF:

0.382

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.253

Gnomad OTH exome

AF:

0.276

GnomAD4 exome

AF:

0.270

AC:

393595

AN:

1459906

Hom.:

56215

Cov.:

AF XY:

0.273

AC XY:

198473

AN XY:

726260

show subpopulations

Gnomad4 AFR exome

AF:

0.158

Gnomad4 AMR exome

AF:

0.338

Gnomad4 ASJ exome

AF:

0.242

Gnomad4 EAS exome

AF:

0.543

Gnomad4 SAS exome

AF:

0.385

Gnomad4 FIN exome

AF:

0.257

Gnomad4 NFE exome

AF:

0.253

Gnomad4 OTH exome

AF:

0.274

GnomAD4 genome

AF:

0.243

AC:

37002

AN:

151990

Hom.:

5044

Cov.:

AF XY:

0.247

AC XY:

18356

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.157

Gnomad4 AMR

AF:

0.282

Gnomad4 ASJ

AF:

0.236

Gnomad4 EAS

AF:

0.471

Gnomad4 SAS

AF:

0.414

Gnomad4 FIN

AF:

0.251

Gnomad4 NFE

AF:

0.256

Gnomad4 OTH

AF:

0.233

Alfa

AF:

0.223

Hom.:

1333

Bravo

AF:

0.239

ESP6500AA

AF:

0.155

AC:

685

ESP6500EA

AF:

0.248

AC:

2132

ExAC

AF:

0.285

AC:

34590

EpiCase

AF:

0.258

EpiControl

AF:

0.250

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 23, 2016	- -

Clubfoot

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Brachydactyly-elbow wrist dysplasia syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.071

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

.;T

MetaRNN

Benign

0.0028

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.045

N;N

MutationTaster

Benign

0.000082

P;P

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.98

N;N

REVEL

Uncertain

0.36

Sift

Benign

0.75

T;T

Sift4G

Benign

0.77

T;T

Polyphen

0.15

B;B

Vest4

0.076

MPC

1.1

ClinPred

0.030

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.10

gMVP

0.42

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over