rs140850664

Positions:

• chr11-72244023-C-G
• chr11-72244023-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005169.4(PHOX2A):​c.-19G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.000035 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00064 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PHOX2A NM_005169.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.62

Genes affected

PHOX2A (HGNC:691): (paired like homeobox 2A) The protein encoded by this gene contains a paired-like homeodomain most similar to that of the Drosophila aristaless gene product. The encoded protein plays a central role in development of the autonomic nervous system. It regulates the expression of tyrosine hydroxylase and dopamine beta-hydroxylase, two catecholaminergic biosynthetic enzymes essential for the differentiation and maintenance of the noradrenergic neurotransmitter phenotype. The encoded protein has also been shown to regulate transcription of the alpha3 nicotinic acetylcholine receptor gene. Mutations in this gene have been associated with autosomal recessive congenital fibrosis of the extraocular muscles. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHOX2A	NM_005169.4	c.-19G>C		5_prime_UTR_variant	1/3	ENST00000298231.5
PHOX2A	XM_047426947.1	c.-19G>C		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHOX2A	ENST00000298231.5	c.-19G>C		5_prime_UTR_variant	1/3	1	NM_005169.4	P1
PHOX2A	ENST00000544057.1	n.85+1557G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 4 AN: 112762 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.0000325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000835

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000385

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000643 AC: 171 AN: 265900 Hom.: 0 Cov.: 6 AF XY: 0.000668 AC XY: 85 AN XY: 127282

Gnomad4 AFR exome AF: 0.000176

Gnomad4 AMR exome AF: 0.000309

Gnomad4 ASJ exome AF: 0.000739

Gnomad4 EAS exome AF: 0.00101

Gnomad4 SAS exome AF: 0.000480

Gnomad4 FIN exome AF: 0.00263

Gnomad4 NFE exome AF: 0.000539

Gnomad4 OTH exome AF: 0.000204

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000355 AC: 4 AN: 112762 Hom.: 0 Cov.: 30 AF XY: 0.0000180 AC XY: 1 AN XY: 55604

Gnomad4 AFR AF: 0.0000325

Gnomad4 AMR AF: 0.0000835

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000385

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	19
DANN	Benign	0.76

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: rs140850664; hg19: chr11-71955067;