Variant chr4-70033188-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000200.3(HTN3):c.124G>C(p.Gly42Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00398 in 1,606,366 control chromosomes in the GnomAD database, including 196 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 Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 109 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 87 hom. )

Consequence

HTN3
NM_000200.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.168

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:

HTN3 (HGNC:):

HTN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026881099).

BP6

Variant 4-70033188-G-C is Benign according to our data. Variant chr4-70033188-G-C is described in ClinVar as [Benign]. Clinvar id is 767955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTN3	NM_000200.3 linkuse as main transcript	c.124G>C	p.Gly42Arg	missense_variant	5/6	ENST00000673563.1	NP_000191.1	P15516

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTN3	ENST00000673563.1 linkuse as main transcript	c.124G>C	p.Gly42Arg	missense_variant	5/6		NM_000200.3	ENSP00000500623.1		P15516

Frequencies

GnomAD3 genomes

AF:

0.0212

AC:

3217

AN:

151936

Hom.:

103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0733

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00760

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00535

AC:

1329

AN:

248630

Hom.:

AF XY:

0.00401

AC XY:

539

AN XY:

134468

show subpopulations

Gnomad AFR exome

AF:

0.0739

Gnomad AMR exome

AF:

0.00267

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000332

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000221

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.00216

AC:

3144

AN:

1454312

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

1368

AN XY:

723670

show subpopulations

Gnomad4 AFR exome

AF:

0.0716

Gnomad4 AMR exome

AF:

0.00336

Gnomad4 ASJ exome

AF:

0.00173

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000152

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000232

Gnomad4 OTH exome

AF:

0.00511

GnomAD4 genome

AF:

0.0213

AC:

3242

AN:

152054

Hom.:

109

Cov.:

AF XY:

0.0203

AC XY:

1506

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0737

Gnomad4 AMR

AF:

0.00759

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.00609

Hom.:

Bravo

AF:

0.0250

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0706

AC:

311

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00662

AC:

804

Asia WGS

AF:

0.00751

AC:

AN:

3476

EpiCase

AF:

0.000219

EpiControl

AF:

0.000417

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.62

CADD

Benign

6.6

DANN

Benign

0.23

DEOGEN2

Benign

0.0047

T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0013

MetaRNN

Benign

0.0027

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.24

PROVEAN

Pathogenic

-5.1

D;D;D

REVEL

Benign

0.041

Sift

Uncertain

0.020

D;D;D

Sift4G

Uncertain

0.030

D;D;D

Polyphen

0.087

B;B;.

Vest4

0.25

MVP

0.14

MPC

0.030

ClinPred

0.019

GERP RS

-2.2

Varity_R

0.15

gMVP

0.013

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over