rs17147990

chr4-70033205-T-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM4 BA1

The NM_000200.3(HTN3):c.141T>A(p.Tyr47Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00781 in 1,599,504 control chromosomes in the GnomAD database, including 901 homozygotes. In-silico tool predicts 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 (503 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (398 hom.)
• Consequence: HTN3 NM_000200.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318

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 Likely_benign. Variant got -6 ACMG points.

• PM4: Stoplost variant in NM_000200.3 Downstream stopcodon found after 74 codons.
• 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.141T>A	p.Tyr47Ter	stop_gained	5/6	ENST00000673563.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTN3	ENST00000673563.1	c.141T>A	p.Tyr47Ter	stop_gained	5/6		NM_000200.3	A2

Frequencies

GnomAD3 genomes AF: 0.0441 AC: 6705 AN: 152054 Hom.: 500 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0161

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0321

GnomAD3 exomes AF: 0.0104 AC: 2569 AN: 246454 Hom.: 167 AF XY: 0.00724 AC XY: 965 AN XY: 133294

Gnomad AFR exome AF: 0.149

Gnomad AMR exome AF: 0.00552

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000204

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000186

Gnomad OTH exome AF: 0.00318

GnomAD4 exome AF: 0.00399 AC: 5775 AN: 1447332 Hom.: 398 Cov.: 28 AF XY: 0.00334 AC XY: 2404 AN XY: 720424

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.00698

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000260

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000680

Gnomad4 OTH exome AF: 0.00949

GnomAD4 genome AF: 0.0442 AC: 6719 AN: 152172 Hom.: 503 Cov.: 32 AF XY: 0.0426 AC XY: 3170 AN XY: 74406

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.0160

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0318

Alfa AF: 0.00666 Hom.: 55

Bravo AF: 0.0500

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.145 AC: 641

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.0137 AC: 1667

Asia WGS AF: 0.0100 AC: 35 AN: 3478

EpiCase AF: 0.000110

EpiControl AF: 0.000179

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.20
Cadd	Pathogenic	35
Dann	Benign	0.89
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.0045	N
MutationTaster	Benign	1.0	P;P;P
Vest4		0.43
GERP RS		-2.8

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

Publications

LitVar

Other links and lift over

dbSNP: rs17147990; hg19: chr4-70898922;