ENST00000244302.8:n.2014A>C

Variant names:

• chr19-46331426-A-C
• rs11665853
• ENST00000244302.8:n.2014A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000244302.8(HIF3A):​n.2014A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 28)
• Consequence: HIF3A ENST00000244302.8 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.560
• Publications: 6 publications found

Genes affected

HIF3A (HGNC:15825): (hypoxia inducible factor 3 subunit alpha) The protein encoded by this gene is the alpha-3 subunit of one of several alpha/beta-subunit heterodimeric transcription factors that regulate many adaptive responses to low oxygen tension (hypoxia). The alpha-3 subunit lacks the transactivation domain found in factors containing either the alpha-1 or alpha-2 subunits. It is thought that factors containing the alpha-3 subunit are negative regulators of hypoxia-inducible gene expression. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2011]

ENSG00000269124 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000244302.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIF3A	NM_152795.4	MANE Select	c.1830+153A>C		intron	N/A	NP_690008.2
	HIF3A	NM_152794.4		c.1824+153A>C		intron	N/A	NP_690007.1
	HIF3A	NM_022462.4		c.1623+153A>C		intron	N/A	NP_071907.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIF3A	ENST00000244302.8	TSL:1	n.2014A>C		non_coding_transcript_exon	Exon 13 of 13
	HIF3A	ENST00000377670.9	TSL:1 MANE Select	c.1830+153A>C		intron	N/A	ENSP00000366898.3
	HIF3A	ENST00000300862.7	TSL:1	c.1824+153A>C		intron	N/A	ENSP00000300862.3

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 5

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 2673

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.93
DANN	Benign	0.73
PhyloP100		-0.56

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: rs11665853; hg19: chr19-46834683;