X-66164321-C-T

Variant names:

• chrX-66164321-C-T
• rs1028348
• NM_001367233.3:c.-163C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367233.3(HEPH):​c.-163C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 750,884 control chromosomes in the GnomAD database, including 9,497 homozygotes. There are 31,242 hemizygotes in GnomAD. 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: 𝑓 0.25 (4639 hom., 7616 hem., cov: 22)
  • Exomes 𝑓: 0.12 (4858 hom. 23626 hem.)
• Consequence: HEPH NM_001367233.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEPH	NM_001367233.3	c.-163C>T		5_prime_UTR_variant	Exon 1 of 21	ENST00000343002.7	NP_001354162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEPH	ENST00000343002	c.-163C>T		5_prime_UTR_variant	Exon 1 of 21	1	NM_001367233.3	ENSP00000343939.2

Frequencies

GnomAD3 genomes AF: 0.251 AC: 27671 AN: 110460 Hom.: 4639 Cov.: 22 AF XY: 0.231 AC XY: 7575 AN XY: 32728

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.00140

Gnomad SAS AF: 0.0793

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0711

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.125 AC: 79890 AN: 640371 Hom.: 4858 Cov.: 22 AF XY: 0.123 AC XY: 23626 AN XY: 192033

Gnomad4 AFR exome AF: 0.646

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0985

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.251 AC: 27717 AN: 110513 Hom.: 4639 Cov.: 22 AF XY: 0.232 AC XY: 7616 AN XY: 32791

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.00141

Gnomad4 SAS AF: 0.0803

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.190

Alfa AF: 0.124 Hom.: 6344

Bravo AF: 0.273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.2
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1028348; hg19: chrX-65384163;