X-66162843-T-A

Variant names:

• chrX-66162843-T-A
• rs5919015
• ENST00000519389.6:c.-47T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138737.6(HEPH):​c.-47T>A variant causes a 5 prime UTR 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: 22)
• Consequence: HEPH NM_138737.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• Publications: 28 publications found

Genes affected

HEPH (HGNC:4866): (hephaestin) This gene encodes a member of the multicopper oxidase protein family. The encoded protein is involved in the transport of dietary iron from epithelial cells of the intestinal lumen into the circulatory system, and may be involved in copper transport and homeostasis. In mouse, defects in this gene can lead to severe microcytic anemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

HEPH Gene-Disease associations (from GenCC):

• hereditary hemochromatosis

  Inheritance: XL Classification: MODERATE Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.087638885).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138737.6. 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
	HEPH	NM_138737.6		c.-47T>A		5_prime_UTR	Exon 1 of 21	NP_620074.4	Q9BQS7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEPH	ENST00000519389.6	TSL:1	c.-47T>A		5_prime_UTR	Exon 1 of 21	ENSP00000430620.2	Q9BQS7-1
	HEPH	ENST00000887532.1		c.-47T>A		5_prime_UTR	Exon 1 of 22	ENSP00000557591.1
	HEPH	ENST00000887519.1		c.-69T>A		5_prime_UTR	Exon 1 of 21	ENSP00000557578.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 121838

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	3.3
DANN	Benign	0.56
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.088	T
MetaSVM	Uncertain	0.41	D
PhyloP100		-0.18
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.19
Sift	Uncertain	0.011	D
Sift4G	Benign	0.072	T
Vest4		0.15
MutPred		0.52		Gain of solvent accessibility (P = 9e-04)
MVP		0.32
MPC		0.13
ClinPred		0.046	T
GERP RS		-4.4
PromoterAI		-0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.54
Mutation Taster		=98/2	polymorphism

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: rs5919015; hg19: chrX-65382685;