5-135034102-C-A

Position:

• chr5-135034102-C-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.-221G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0549 in 165,788 control chromosomes in the GnomAD database, including 396 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.052 (331 hom., cov: 31)
  • Exomes 𝑓: 0.083 (65 hom.)
• Consequence: PITX1 NM_002653.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.45

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=-0.77).
• BP6: Variant 5-135034102-C-A is Benign according to our data. Variant chr5-135034102-C-A is described in ClinVar as [Benign]. Clinvar id is 1274487.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITX1	NM_002653.5	c.-221G>T		5_prime_UTR_variant	1/3	ENST00000265340.12	NP_002644.4
PITX1-AS1	NR_161235.1	n.267+562C>A		intron_variant, non_coding_transcript_variant
PITX1	XM_047417318.1	c.35-153G>T		intron_variant			XP_047273274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITX1	ENST00000265340.12	c.-221G>T		5_prime_UTR_variant	1/3	1	NM_002653.5	ENSP00000265340	P1
PITX1-AS1	ENST00000624272.3	n.261+562C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0522 AC: 7850 AN: 150334 Hom.: 331 Cov.: 31

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.0698

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.000393

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.0623

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.0703

Gnomad OTH AF: 0.0630

GnomAD4 exome AF: 0.0826 AC: 1267 AN: 15346 Hom.: 65 Cov.: 0 AF XY: 0.0822 AC XY: 694 AN XY: 8440

Gnomad4 AFR exome AF: 0.0145

Gnomad4 AMR exome AF: 0.0625

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0128

Gnomad4 FIN exome AF: 0.0800

Gnomad4 NFE exome AF: 0.0863

Gnomad4 OTH exome AF: 0.0854

GnomAD4 genome AF: 0.0521 AC: 7843 AN: 150442 Hom.: 331 Cov.: 31 AF XY: 0.0519 AC XY: 3815 AN XY: 73502

Gnomad4 AFR AF: 0.0119

Gnomad4 AMR AF: 0.0697

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.000394

Gnomad4 SAS AF: 0.0131

Gnomad4 FIN AF: 0.0623

Gnomad4 NFE AF: 0.0703

Gnomad4 OTH AF: 0.0623

Alfa AF: 0.0560 Hom.: 48

Bravo AF: 0.0520

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	-0.77
CADD	Benign	12
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs113986847; hg19: chr5-134369792;