Variant X-66162843-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The ENST00000519389.6(HEPH):c.-47T>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. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.80 ( 25410 hom., 25897 hem., cov: 22)

Exomes 𝑓: 0.71 ( 178935 hom. 244428 hem. )

Failed GnomAD Quality Control

Consequence

HEPH
ENST00000519389.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.179

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.7057484E-6).

BP6

Variant X-66162843-T-C is Benign according to our data. Variant chrX-66162843-T-C is described in ClinVar as [Benign]. Clinvar id is 3256843.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
HEPH	XM_011531073.4 linkuse as main transcript	c.116T>C	p.Val39Ala	missense_variant	1/21
HEPH	XM_047442694.1 linkuse as main transcript	c.79T>C	p.Cys27Arg	missense_variant	1/21
HEPH	XM_011531074.3 linkuse as main transcript	c.116T>C	p.Val39Ala	missense_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEPH	ENST00000519389.6 linkuse as main transcript	c.-47T>C		5_prime_UTR_variant	1/21	1		P5	Q9BQS7-1

Frequencies

GnomAD3 genomes

AF:

0.799

AC:

87891

AN:

109943

Hom.:

25409

Cov.:

AF XY:

0.804

AC XY:

25834

AN XY:

32141

show subpopulations

Gnomad AFR

AF:

0.957

Gnomad AMI

AF:

0.641

Gnomad AMR

AF:

0.875

Gnomad ASJ

AF:

0.867

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.924

Gnomad FIN

AF:

0.731

Gnomad MID

AF:

0.900

Gnomad NFE

AF:

0.680

Gnomad OTH

AF:

0.841

GnomAD3 exomes

AF:

0.812

AC:

83724

AN:

103057

Hom.:

22370

AF XY:

0.812

AC XY:

30125

AN XY:

37113

show subpopulations

Gnomad AFR exome

AF:

0.965

Gnomad AMR exome

AF:

0.913

Gnomad ASJ exome

AF:

0.865

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.911

Gnomad FIN exome

AF:

0.717

Gnomad NFE exome

AF:

0.680

Gnomad OTH exome

AF:

0.813

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.710

AC:

740343

AN:

1042502

Hom.:

178935

Cov.:

AF XY:

0.717

AC XY:

244428

AN XY:

341134

show subpopulations

Gnomad4 AFR exome

AF:

0.964

Gnomad4 AMR exome

AF:

0.910

Gnomad4 ASJ exome

AF:

0.865

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.909

Gnomad4 FIN exome

AF:

0.723

Gnomad4 NFE exome

AF:

0.666

Gnomad4 OTH exome

AF:

0.762

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.800

AC:

87951

AN:

109998

Hom.:

25410

Cov.:

AF XY:

0.804

AC XY:

25897

AN XY:

32206

show subpopulations

Gnomad4 AFR

AF:

0.957

Gnomad4 AMR

AF:

0.875

Gnomad4 ASJ

AF:

0.867

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.924

Gnomad4 FIN

AF:

0.731

Gnomad4 NFE

AF:

0.680

Gnomad4 OTH

AF:

0.843

Alfa

AF:

0.721

Hom.:

95930

Bravo

AF:

0.822

TwinsUK

AF:

0.666

AC:

2470

ALSPAC

AF:

0.656

AC:

1894

ESP6500AA

AF:

0.968

AC:

1170

ESP6500EA

AF:

0.689

AC:

1647

ExAC

AF:

0.826

AC:

15731

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 31, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 90% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 84. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

3.7

DANN

Benign

0.54

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.12

MetaRNN

Benign

0.0000017

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.25

PROVEAN

Benign

0.27

REVEL

Benign

0.16

Sift

Benign

1.0

Sift4G

Benign

0.81

Vest4

0.011

MPC

0.096

ClinPred

0.0035

GERP RS

-4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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