5-135033568-G-A

Position:

• chr5-135033568-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002653.5(PITX1):​c.169+145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 845,952 control chromosomes in the GnomAD database, including 4,936 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.099 (814 hom., cov: 32)
  • Exomes 𝑓: 0.10 (4122 hom.)
• Consequence: PITX1 NM_002653.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.578

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-AS1 (HGNC:48332): (PITX1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 5-135033568-G-A is Benign according to our data. Variant chr5-135033568-G-A is described in ClinVar as [Benign]. Clinvar id is 1278728.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PITX1	NM_002653.5	c.169+145C>T		intron_variant		ENST00000265340.12
PITX1-AS1	NR_161235.1	n.267+28G>A		intron_variant, non_coding_transcript_variant
PITX1	XM_047417318.1	c.271+145C>T		intron_variant
PITX1	XM_047417319.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PITX1	ENST00000265340.12	c.169+145C>T		intron_variant		1	NM_002653.5	P1
PITX1-AS1	ENST00000624272.3	n.261+28G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0984 AC: 14968 AN: 152160 Hom.: 804 Cov.: 32

Gnomad AFR AF: 0.0803

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0478

Gnomad FIN AF: 0.0754

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.102 AC: 70636 AN: 693674 Hom.: 4122 Cov.: 9 AF XY: 0.0992 AC XY: 35920 AN XY: 362000

Gnomad4 AFR exome AF: 0.0770

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.0635

Gnomad4 EAS exome AF: 0.0000656

Gnomad4 SAS exome AF: 0.0480

Gnomad4 FIN exome AF: 0.0803

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.0960

GnomAD4 genome AF: 0.0985 AC: 15007 AN: 152278 Hom.: 814 Cov.: 32 AF XY: 0.0956 AC XY: 7118 AN XY: 74456

Gnomad4 AFR AF: 0.0803

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.0620

Gnomad4 EAS AF: 0.00175

Gnomad4 SAS AF: 0.0489

Gnomad4 FIN AF: 0.0754

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.105

Alfa AF: 0.100 Hom.: 110

Bravo AF: 0.104

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Uncertain	0.98

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

Other links and lift over

dbSNP: rs72800397; hg19: chr5-134369258;