4-70033186-GA-AG

Variant names:

• chr4-70033186-GA-AG
• NM_000200.3:c.122_123delGAinsAG
• HTN3 p.Arg41Gln

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM1

The NM_000200.3(HTN3):​c.122_123delGAinsAG​(p.Arg41Gln) variant causes a missense 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: HTN3 NM_000200.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• Publications: 0 publications found

Genes affected

HTN3 (HGNC:5284): (histatin 3) This gene encodes a member of the histatin family of small, histidine-rich, cationic proteins. They function as antimicrobial peptides and are important components of the innate immune system. Histatins are found in saliva and exhibit antibacterial, antifungal activities and function in wound healing. [provided by RefSeq, Sep 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM1: In a mutagenesis_site 10-fold reduction in candidacidal activity of His3-(20-43)-peptide; when associated with E-32. (size 0) in uniprot entity HIS3_HUMAN

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000200.3. 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
	HTN3	NM_000200.3	MANE Select	c.122_123delGAinsAG	p.Arg41Gln	missense	N/A	NP_000191.1	P15516

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTN3	ENST00000673563.1	MANE Select	c.122_123delGAinsAG	p.Arg41Gln	missense	N/A	ENSP00000500623.1	P15516
	HTN3	ENST00000530128.5	TSL:2	c.122_123delGAinsAG	p.Arg41Gln	missense	N/A	ENSP00000432561.1	P15516
	HTN3	ENST00000381057.3	TSL:2	c.92_93delGAinsAG	p.Arg31Gln	missense	N/A	ENSP00000370445.3	X6RAH8

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		0.068

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: chr4-70898903;