Variant 12-53506856-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003717.4(NPFF):c.262T>C(p.Trp88Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00444 in 1,604,760 control chromosomes in the GnomAD database, including 157 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.019 ( 71 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 86 hom. )

Consequence

NPFF
NM_003717.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.829

Variant links:

Genes affected

NPFF (HGNC:7901): (neuropeptide FF-amide peptide precursor) This gene encodes a member of the FMRFamide related peptide (FARP) family of neuropeptides. The encoded preproprotein is proteolytically processed to generate multiple amidated peptides. These peptides may play a role in the regulation of heart rate and blood pressure and the modulation of morphine-induced antinociception. Patients with hypertension exhibit decreased expression of the encoded protein. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

NPFF links:

ATF7-NPFF (HGNC:):

ATF7-NPFF links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015759766).

BP6

Variant 12-53506856-A-G is Benign according to our data. Variant chr12-53506856-A-G is described in ClinVar as [Benign]. Clinvar id is 776710.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPFF	NM_003717.4 linkuse as main transcript	c.262T>C	p.Trp88Arg	missense_variant	3/3	ENST00000267017.4
ATF7-NPFF	NR_159377.1 linkuse as main transcript	n.2053T>C		non_coding_transcript_exon_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPFF	ENST00000267017.4 linkuse as main transcript	c.262T>C	p.Trp88Arg	missense_variant	3/3	1	NM_003717.4	P1	O15130-1
NPFF	ENST00000448979.4 linkuse as main transcript	n.502T>C		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes

AF:

0.0191

AC:

2901

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0631

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0279

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.0125

GnomAD3 exomes

AF:

0.00728

AC:

1769

AN:

242936

Hom.:

AF XY:

0.00584

AC XY:

765

AN XY:

131086

show subpopulations

Gnomad AFR exome

AF:

0.0637

Gnomad AMR exome

AF:

0.00252

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0299

Gnomad SAS exome

AF:

0.00141

Gnomad FIN exome

AF:

0.0000472

Gnomad NFE exome

AF:

0.000464

Gnomad OTH exome

AF:

0.00323

GnomAD4 exome

AF:

0.00291

AC:

4229

AN:

1452502

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

1918

AN XY:

721782

show subpopulations

Gnomad4 AFR exome

AF:

0.0597

Gnomad4 AMR exome

AF:

0.00248

Gnomad4 ASJ exome

AF:

0.0000788

Gnomad4 EAS exome

AF:

0.0293

Gnomad4 SAS exome

AF:

0.00136

Gnomad4 FIN exome

AF:

0.0000377

Gnomad4 NFE exome

AF:

0.000494

Gnomad4 OTH exome

AF:

0.00502

GnomAD4 genome

AF:

0.0191

AC:

2904

AN:

152258

Hom.:

Cov.:

AF XY:

0.0177

AC XY:

1321

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0629

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0279

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00455

Hom.:

Bravo

AF:

0.0209

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0631

AC:

278

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00830

AC:

1007

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

0.073

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.7

DANN

Benign

0.77

DEOGEN2

Benign

0.0085

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0078

LIST_S2

Benign

0.097

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

4.8

REVEL

Benign

0.044

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.031

MutPred

0.10

Loss of catalytic residue at P91 (P = 0.0269);

MVP

0.072

MPC

0.40

ClinPred

0.0013

GERP RS

-2.8

Varity_R

0.049

gMVP

0.018

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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