rs5919015

Positions:

• chrX-66162843-T-A
• chrX-66162843-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000519389.6(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 ENST00000519389.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEPH	XM_011531073.4	c.116T>A	p.Val39Glu	missense_variant	1/21		XP_011529375.1
HEPH	XM_047442694.1	c.79T>A	p.Cys27Ser	missense_variant	1/21		XP_047298650.1
HEPH	XM_011531074.3	c.116T>A	p.Val39Glu	missense_variant	1/20		XP_011529376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEPH	ENST00000519389.6	c.-47T>A		5_prime_UTR_variant	1/21	1		ENSP00000430620	P5

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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
MutationTaster	Benign	1.0	P;P
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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.54

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: rs5919015; hg19: chrX-65382685;