Variant 16-4588221-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145011.2(C16orf96):c.2482G>A(p.Val828Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000599 in 1,551,702 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

C16orf96
NM_001145011.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00900

Variant links:

Genes affected

C16orf96 (HGNC:40031): (chromosome 16 open reading frame 96)

C16orf96 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02809745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C16orf96	NM_001145011.2 link	c.2482G>A	p.Val828Met	missense_variant	9/16	ENST00000444310.5	NP_001138483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C16orf96	ENST00000444310.5 link	c.2482G>A	p.Val828Met	missense_variant	9/16	5	NM_001145011.2	ENSP00000415027.3		A6NNT2

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000130

AC:

AN:

154050

Hom.:

AF XY:

0.000147

AC XY:

AN XY:

81744

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000729

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000168

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.0000300

AC:

AN:

1399364

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

690200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000588

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000148

Gnomad4 OTH exome

AF:

0.0000862

GnomAD4 genome

AF:

0.000335

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.000208

ExAC

AF:

0.0000420

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.2482G>A (p.V828M) alteration is located in exon 9 (coding exon 9) of the C16orf96 gene. This alteration results from a G to A substitution at nucleotide position 2482, causing the valine (V) at amino acid position 828 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.60

CADD

Benign

9.0

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0044

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.50

M_CAP

Benign

0.031

MetaRNN

Benign

0.028

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PROVEAN

Benign

-1.6

REVEL

Benign

0.078

Sift

Benign

0.071

Sift4G

Benign

0.15

Polyphen

0.24

Vest4

0.10

MutPred

0.30

Gain of catalytic residue at V828 (P = 0.0215);

MVP

0.030

ClinPred

0.049

GERP RS

-0.94

Varity_R

0.032

gMVP

0.14

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