Genetic Variant HTN3:p.Thr17Ile (chr4-70030790-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_000200.3(HTN3):c.50C>T(p.Thr17Ile) 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. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

HTN3
NM_000200.3 missense, splice_region

Scores

Splicing: ADA: 0.0001046

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.87

Publications

0 publications found

Variant links:

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]

HTN3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15521115).

BP6

Variant 4-70030790-C-T is Benign according to our data. Variant chr4-70030790-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3107473.Status of the report is criteria_provided_single_submitter, 1 stars.

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.50C>T	p.Thr17Ile	missense splice_region	Exon 2 of 6	NP_000191.1	P15516

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HTN3	ENST00000673563.1	MANE Select	c.50C>T	p.Thr17Ile	missense splice_region	Exon 2 of 6	ENSP00000500623.1	P15516
HTN3	ENST00000530128.5	TSL:2	c.50C>T	p.Thr17Ile	missense splice_region	Exon 2 of 6	ENSP00000432561.1	P15516
HTN3	ENST00000381057.3	TSL:2	c.50C>T	p.Thr17Ile	missense splice_region	Exon 2 of 5	ENSP00000370445.3	X6RAH8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251004

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.040

(source)

DANN

Benign

0.40

DEOGEN2

Benign

0.0023

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.0029

M_CAP

Benign

0.0027

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

PhyloP100

-1.9

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.060

Sift

Benign

0.17

Sift4G

Benign

0.30

Polyphen

0.11

Vest4

0.14

MutPred

0.19

Loss of disorder (P = 0.0531)

MVP

0.22

MPC

0.022

ClinPred

0.073

GERP RS

-4.3

Varity_R

0.066

gMVP

0.0099

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.018

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over