rs1136511

chr4-70033186-G-A

Variant summary

Our verdict is Benign. Variant got -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. 13/19 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTN3	NM_000200.3	c.122G>A	p.Arg41Gln	missense_variant	5/6	ENST00000673563.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTN3	ENST00000673563.1	c.122G>A	p.Arg41Gln	missense_variant	5/6		NM_000200.3	A2

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

GnomAD3 exomes AF: 0.0111 AC: 2760 AN: 248408 Hom.: 179 AF XY: 0.00806 AC XY: 1083 AN XY: 134382

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 SAS exome AF: 0.00389

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

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.00712

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00373

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.0000822

Gnomad4 OTH exome AF: 0.00987

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

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.0161

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0318

Alfa AF: 0.0174 Hom.: 97

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 v4.3

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;T;T
Eigen	Benign	-0.84
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0032	N
MetaRNN	Benign	0.0015	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Benign	0.073
Sift	Benign	0.079	T;T;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.54	P;P;.
Vest4		0.16
MPC		0.024
ClinPred		0.019	T
GERP RS		0.31
Varity_R		0.053
gMVP		0.022

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

Publications

LitVar

Other links and lift over

dbSNP: rs1136511; hg19: chr4-70898903;