chr5-135032413-A-T

Variant names:

• chr5-135032413-A-T
• rs6596188
• NM_002653.5:c.170-905T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002653.5(PITX1):​c.170-905T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,210 control chromosomes in the GnomAD database, including 4,608 homozygotes. 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: 𝑓 0.20 (4608 hom., cov: 33)
• Consequence: PITX1 NM_002653.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.707
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• clubfoot

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• brachydactyly-elbow wrist dysplasia syndrome

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

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.170-905T>A		intron	N/A	NP_002644.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITX1	ENST00000265340.12	TSL:1 MANE Select	c.170-905T>A		intron	N/A	ENSP00000265340.6	P78337
	PITX1	ENST00000506438.5	TSL:1	c.170-905T>A		intron	N/A	ENSP00000427542.1	P78337
	PITX1	ENST00000507253.5	TSL:3	c.170-905T>A		intron	N/A	ENSP00000422908.1	D6R9U1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30236 AN: 152092 Hom.: 4573 Cov.: 33

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0496

Gnomad FIN AF: 0.0756

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.191

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.199 AC: 30344 AN: 152210 Hom.: 4608 Cov.: 33 AF XY: 0.192 AC XY: 14299 AN XY: 74430

African (AFR) AF: 0.424 AC: 17577 AN: 41486

American (AMR) AF: 0.207 AC: 3161 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0671 AC: 233 AN: 3470

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5188

South Asian (SAS) AF: 0.0509 AC: 245 AN: 4816

European-Finnish (FIN) AF: 0.0756 AC: 802 AN: 10612

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7871 AN: 68028

Other (OTH) AF: 0.189 AC: 399 AN: 2112

Alfa AF: 0.0683 Hom.: 104

Bravo AF: 0.221

Asia WGS AF: 0.0520 AC: 182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.5
DANN	Benign	0.32
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6596188; hg19: chr5-134368103;