Genetic Variant C16orf96:p.Arg484Cys (chr16-4575930-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001145011.2(C16orf96):c.1450C>T(p.Arg484Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00353 in 1,536,462 control chromosomes in the GnomAD database, including 42 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 36 hom. )

Consequence

C16orf96
NM_001145011.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.82

Publications

5 publications found

Variant links:

Genes affected

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

C16orf96 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005681157).

BP6

Variant 16-4575930-C-T is Benign according to our data. Variant chr16-4575930-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 771013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00311 (4300/1384236) while in subpopulation MID AF = 0.0219 (122/5580). AF 95% confidence interval is 0.0187. There are 36 homozygotes in GnomAdExome4. There are 2217 alleles in the male GnomAdExome4 subpopulation. Median coverage is 36. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145011.2. 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
	C16orf96	NM_001145011.2	MANE Select	c.1450C>T	p.Arg484Cys	missense	Exon 5 of 16	NP_001138483.1	A6NNT2
	C16orf96	NM_001387219.1		c.1450C>T	p.Arg484Cys	missense	Exon 7 of 18	NP_001374148.1	A6NNT2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C16orf96	ENST00000444310.5	TSL:5 MANE Select	c.1450C>T	p.Arg484Cys	missense	Exon 5 of 16	ENSP00000415027.3	A6NNT2

Frequencies

GnomAD3 genomes

AF:

0.00738

AC:

1122

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0117

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0127

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00916

Gnomad OTH

AF:

0.0172

GnomAD2 exomes

AF:

0.00361

AC:

552

AN:

152864

AF XY:

0.00334

show subpopulations

Gnomad AFR exome

AF:

0.00114

Gnomad AMR exome

AF:

0.00236

Gnomad ASJ exome

AF:

0.00424

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00859

Gnomad NFE exome

AF:

0.00501

Gnomad OTH exome

AF:

0.00351

GnomAD4 exome

AF:

0.00311

AC:

4300

AN:

1384236

Hom.:

Cov.:

AF XY:

0.00325

AC XY:

2217

AN XY:

683066

show subpopulations

African (AFR)

AF:

0.00105

AC:

AN:

31526

American (AMR)

AF:

0.00442

AC:

157

AN:

35560

Ashkenazi Jewish (ASJ)

AF:

0.00981

AC:

243

AN:

24774

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35736

South Asian (SAS)

AF:

0.00110

AC:

AN:

79178

European-Finnish (FIN)

AF:

0.0126

AC:

617

AN:

49082

Middle Eastern (MID)

AF:

0.0219

AC:

122

AN:

5580

European-Non Finnish (NFE)

AF:

0.00258

AC:

2752

AN:

1065282

Other (OTH)

AF:

0.00501

AC:

288

AN:

57518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

352

703

1055

1406

1758

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00736

AC:

1121

AN:

152226

Hom.:

Cov.:

AF XY:

0.00715

AC XY:

532

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.00178

AC:

AN:

41560

American (AMR)

AF:

0.0116

AC:

178

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0159

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0127

AC:

135

AN:

10612

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00916

AC:

623

AN:

67988

Other (OTH)

AF:

0.0171

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

108

163

217

271

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00836

Hom.:

Bravo

AF:

0.00780

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.0113

AC:

ExAC

AF:

0.00568

AC:

127

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0053

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.0023

LIST_S2

Benign

0.64

MetaRNN

Benign

0.0057

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

-1.8

PROVEAN

Benign

-1.8

REVEL

Benign

0.034

Sift

Benign

0.030

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.074

MVP

0.067

ClinPred

0.024

GERP RS

1.6

Varity_R

0.089

gMVP

0.038

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over