rs1136511

Variant names:

• chr4-70033186-G-A
• rs1136511
• NM_000200.3:c.122G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM1 BP4_Strong BA1

The NM_000200.3(HTN3):​c.122G>A​(p.Arg41Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00808 in 1,605,536 control chromosomes in the GnomAD database, including 931 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency:
  • Genomes: 𝑓 0.044 (506 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (425 hom.)
• Consequence: HTN3 NM_000200.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 2 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: Benign. The variant received -10 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
• BP4: Computational evidence support a benign effect (MetaRNN=0.0015038848).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

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.122G>A	p.Arg41Gln	missense	Exon 5 of 6	NP_000191.1	P15516

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTN3	ENST00000673563.1	MANE Select	c.122G>A	p.Arg41Gln	missense	Exon 5 of 6	ENSP00000500623.1	P15516
	HTN3	ENST00000530128.5	TSL:2	c.122G>A	p.Arg41Gln	missense	Exon 5 of 6	ENSP00000432561.1	P15516
	HTN3	ENST00000381057.3	TSL:2	c.92G>A	p.Arg31Gln	missense	Exon 4 of 5	ENSP00000370445.3	X6RAH8

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6745 AN: 151908 Hom.: 503 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00664

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0321

GnomAD2 exomes AF: 0.0111 AC: 2760 AN: 248408 AF XY: 0.00806

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.00575

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000221

Gnomad OTH exome AF: 0.00315

GnomAD4 exome AF: 0.00428 AC: 6220 AN: 1453510 Hom.: 425 Cov.: 28 AF XY: 0.00373 AC XY: 2699 AN XY: 723328

African (AFR) AF: 0.149 AC: 4870 AN: 32578

American (AMR) AF: 0.00712 AC: 315 AN: 44244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26054

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39486

South Asian (SAS) AF: 0.00373 AC: 318 AN: 85258

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53292

Middle Eastern (MID) AF: 0.00487 AC: 28 AN: 5746

European-Non Finnish (NFE) AF: 0.0000822 AC: 91 AN: 1106752

Other (OTH) AF: 0.00987 AC: 593 AN: 60100

GnomAD4 genome AF: 0.0445 AC: 6759 AN: 152026 Hom.: 506 Cov.: 32 AF XY: 0.0430 AC XY: 3194 AN XY: 74310

African (AFR) AF: 0.154 AC: 6399 AN: 41462

American (AMR) AF: 0.0161 AC: 246 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00623 AC: 30 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 67956

Other (OTH) AF: 0.0318 AC: 67 AN: 2110

Alfa AF: 0.0344 Hom.: 414

Bravo AF: 0.0501

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.146 AC: 642

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.0143 AC: 1732

Asia WGS AF: 0.0110 AC: 39 AN: 3476

EpiCase AF: 0.000219

EpiControl AF: 0.000179

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.69
DANN	Benign	0.37
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0032	N
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.1	T
PhyloP100		-1.6
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.073
Sift	Benign	0.079	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.54	P
Vest4		0.16
MPC		0.024
ClinPred		0.019	T
GERP RS		0.31
Varity_R		0.053
gMVP		0.022
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1136511; hg19: chr4-70898903;