Variant chrX-66173643-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001367233.3(HEPH):c.467C>T(p.Pro156Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,478 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

HEPH
NM_001367233.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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=0.1984613).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HEPH	NM_001367233.3 linkuse as main transcript	c.467C>T	p.Pro156Leu	missense_variant	4/21	ENST00000343002.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEPH	ENST00000343002.7 linkuse as main transcript	c.467C>T	p.Pro156Leu	missense_variant	4/21	1	NM_001367233.3	P5	Q9BQS7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097478

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362978

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2023

The c.629C>T (p.P210L) alteration is located in exon 4 (coding exon 4) of the HEPH gene. This alteration results from a C to T substitution at nucleotide position 629, causing the proline (P) at amino acid position 210 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Benign

0.94

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.58

T;T;T;T;T;T

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.20

T;T;T;T;T;T

MetaSVM

Uncertain

0.41

MutationTaster

Benign

0.98

D;D;D;D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-4.7

D;D;D;D;D;D

REVEL

Uncertain

0.35

Sift

Benign

0.40

T;T;T;T;T;T

Sift4G

Benign

0.78

T;T;T;T;T;T

Polyphen

0.0010, 0.74

.;.;.;B;P;.

Vest4

0.25

MutPred

0.39

.;Loss of disorder (P = 0.0173);.;.;Loss of disorder (P = 0.0173);Loss of disorder (P = 0.0173);

MVP

0.71

MPC

0.088

ClinPred

0.20

GERP RS

0.30

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.1

Varity_R

0.11

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over