4-70033188-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.168

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 -14 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_single_submitter, 1 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	UniProt
HTN3	NM_000200.3	c.124G>C	p.Gly42Arg	missense_variant	5/6	ENST00000673563.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTN3	ENST00000673563.1	c.124G>C	p.Gly42Arg	missense_variant	5/6		NM_000200.3	A2

Frequencies

GnomAD3 genomes AF: 0.0212 AC: 3217 AN: 151936 Hom.: 103 Cov.: 32

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.: 45 AF XY: 0.00401 AC XY: 539 AN XY: 134468

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.: 87 Cov.: 28 AF XY: 0.00189 AC XY: 1368 AN XY: 723670

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.: 32 AF XY: 0.0203 AC XY: 1506 AN XY: 74338

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.: 3

Bravo AF: 0.0250

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0706 AC: 311

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00662 AC: 804

Asia WGS AF: 0.00751 AC: 26 AN: 3476

EpiCase AF: 0.000219

EpiControl AF: 0.000417

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.63	T
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	N
MetaRNN	Benign	0.0027	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.24	T
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	T
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

Other links and lift over

dbSNP: rs58376281; hg19: chr4-70898905;