12-12989300-T-A

Variant names:

• chr12-12989300-T-A
• rs1274341125
• NM_015987.5:c.194A>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015987.5(HEBP1):​c.194A>T​(p.Tyr65Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y65C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HEBP1 NM_015987.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.48
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.85

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015987.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEBP1	NM_015987.5	MANE Select	c.194A>T	p.Tyr65Phe	missense	Exon 2 of 4	NP_057071.2
	GPRC5D-AS1	NR_149067.1		n.177+9678T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEBP1	ENST00000014930.9	TSL:1 MANE Select	c.194A>T	p.Tyr65Phe	missense	Exon 2 of 4	ENSP00000014930.4	Q9NRV9
	HEBP1	ENST00000905180.1		c.302A>T	p.Tyr101Phe	missense	Exon 2 of 4	ENSP00000575238.1
	HEBP1	ENST00000905178.1		c.281A>T	p.Tyr94Phe	missense	Exon 2 of 4	ENSP00000575237.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.45
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.24	T
Polyphen		1.0	D
Vest4		0.77
MutPred		0.73		Gain of catalytic residue at A66 (P = 0.0047)
MVP		0.73
MPC		0.57
ClinPred		0.97	D
GERP RS		6.0
PromoterAI		-0.066	Neutral
Varity_R		0.62
gMVP		0.60
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs1274341125; hg19: chr12-13142234;