12-13000061-C-A

Variant names:

• chr12-13000061-C-A
• NM_015987.5:c.54G>T

Variant summary

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

The NM_015987.5(HEBP1):​c.54G>T​(p.Trp18Cys) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HEBP1 NM_015987.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79

Genes affected

HEBP1 (HGNC:17176): (heme binding protein 1) The full-length protein encoded by this gene is an intracellular tetrapyrrole-binding protein. This protein includes a natural chemoattractant peptide of 21 amino acids at the N-terminus, which is a natural ligand for formyl peptide receptor-like receptor 2 (FPRL2) and promotes calcium mobilization and chemotaxis in monocytes and dendritic cells. [provided by RefSeq, Jul 2008]

GPRC5D-AS1 (HGNC:53599): (GPRC5D and HEBP1 antisense RNA 1)

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=0.22806299).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEBP1	NM_015987.5	c.54G>T	p.Trp18Cys	missense_variant	Exon 1 of 4	ENST00000014930.9	NP_057071.2
GPRC5D-AS1	NR_149067.1	n.177+20439C>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEBP1	ENST00000014930.9	c.54G>T	p.Trp18Cys	missense_variant	Exon 1 of 4	1	NM_015987.5	ENSP00000014930.4
HEBP1	ENST00000647702.1	c.112G>T	p.Ala38Ser	missense_variant	Exon 1 of 4			ENSP00000496930.1
HEBP1	ENST00000536942.1	c.54G>T	p.Trp18Cys	missense_variant	Exon 1 of 3	2		ENSP00000441678.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.54G>T (p.W18C) alteration is located in exon 1 (coding exon 1) of the HEBP1 gene. This alteration results from a G to T substitution at nucleotide position 54, causing the tryptophan (W) at amino acid position 18 to be replaced by a cysteine (C). 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	Uncertain	0.43
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Benign	0.14
Eigen_PC	Benign	0.089
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.23	T
ClinPred		0.93	D
GERP RS		3.0

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-13152995;