Variant X-66172339-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001367233.3(HEPH):c.168-16T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,170,780 control chromosomes in the GnomAD database, including 29,981 homozygotes. There are 84,358 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.37 ( 8052 hom., 11133 hem., cov: 22)

Exomes 𝑓: 0.22 ( 21929 hom. 73225 hem. )

Consequence

HEPH
NM_001367233.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0640

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant X-66172339-T-C is Benign according to our data. Variant chrX-66172339-T-C is described in ClinVar as [Benign]. Clinvar id is 3256823.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HEPH	NM_001367233.3 linkuse as main transcript	c.168-16T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000343002.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEPH	ENST00000343002.7 linkuse as main transcript	c.168-16T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001367233.3	P5	Q9BQS7-1

Frequencies

GnomAD3 genomes

AF:

0.365

AC:

40134

AN:

109959

Hom.:

8042

Cov.:

AF XY:

0.344

AC XY:

11089

AN XY:

32249

show subpopulations

Gnomad AFR

AF:

0.774

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.00143

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.221

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.302

GnomAD3 exomes

AF:

0.245

AC:

37247

AN:

152157

Hom.:

5268

AF XY:

0.228

AC XY:

10259

AN XY:

44933

show subpopulations

Gnomad AFR exome

AF:

0.789

Gnomad AMR exome

AF:

0.233

Gnomad ASJ exome

AF:

0.216

Gnomad EAS exome

AF:

0.000959

Gnomad SAS exome

AF:

0.121

Gnomad FIN exome

AF:

0.266

Gnomad NFE exome

AF:

0.216

Gnomad OTH exome

AF:

0.220

GnomAD4 exome

AF:

0.220

AC:

233825

AN:

1060774

Hom.:

21929

Cov.:

AF XY:

0.216

AC XY:

73225

AN XY:

338884

show subpopulations

Gnomad4 AFR exome

AF:

0.796

Gnomad4 AMR exome

AF:

0.241

Gnomad4 ASJ exome

AF:

0.207

Gnomad4 EAS exome

AF:

0.000541

Gnomad4 SAS exome

AF:

0.130

Gnomad4 FIN exome

AF:

0.268

Gnomad4 NFE exome

AF:

0.212

Gnomad4 OTH exome

AF:

0.232

GnomAD4 genome

AF:

0.365

AC:

40190

AN:

110006

Hom.:

8052

Cov.:

AF XY:

0.345

AC XY:

11133

AN XY:

32306

show subpopulations

Gnomad4 AFR

AF:

0.775

Gnomad4 AMR

AF:

0.248

Gnomad4 ASJ

AF:

0.206

Gnomad4 EAS

AF:

0.00143

Gnomad4 SAS

AF:

0.102

Gnomad4 FIN

AF:

0.253

Gnomad4 NFE

AF:

0.218

Gnomad4 OTH

AF:

0.301

Alfa

AF:

0.258

Hom.:

3226

Bravo

AF:

0.383

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 27% 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: 25. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.7

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

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

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