5-157037248-TTT-CTC

Variant names:

• chr5-157037248-TTT-CTC
• NM_001173393.3:c.949_951delAAAinsGAG
• HAVCR1 p.Lys317Glu

Variant summary

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

The NM_001173393.3(HAVCR1):​c.949_951delAAAinsGAG​(p.Lys317Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HAVCR1 NM_001173393.3 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 0 publications found

Genes affected

HAVCR1 (HGNC:17866): (hepatitis A virus cellular receptor 1) The protein encoded by this gene is a membrane receptor for both human hepatitis A virus (HHAV) and TIMD4. The encoded protein may be involved in the moderation of asthma and allergic diseases. The reference genome represents an allele that retains a MTTVP amino acid segment that confers protection against atopy in HHAV seropositive individuals. The protein is a receptor for multiple other viruses, including Ebola virus, Marburg virus, Dengue virus, and Zika virus and is a possible entry factor for SARS-CoV-2 and other coronaviruses. [provided by RefSeq, Sep 2021]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001173393.3. 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
	HAVCR1	NM_001173393.3	MANE Select	c.949_951delAAAinsGAG	p.Lys317Glu	missense splice_region	N/A	NP_001166864.1	Q96D42
	HAVCR1	NM_001308156.2		c.949_951delAAAinsGAG	p.Lys317Glu	missense splice_region	N/A	NP_001295085.1	E9PFX0
	HAVCR1	NM_012206.3		c.949_951delAAAinsGAG	p.Lys317Glu	missense splice_region	N/A	NP_036338.2	B4DPB1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR1	ENST00000523175.6	TSL:1 MANE Select	c.949_951delAAAinsGAG	p.Lys317Glu	missense splice_region	N/A	ENSP00000427898.1	Q96D42
	HAVCR1	ENST00000339252.8	TSL:1	c.949_951delAAAinsGAG	p.Lys317Glu	missense splice_region	N/A	ENSP00000344844.3	Q96D42
	HAVCR1	ENST00000522693.5	TSL:2	c.949_951delAAAinsGAG	p.Lys317Glu	missense splice_region	N/A	ENSP00000428524.1	E9PFX0

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-156464259;