Genetic Variant NM_001145011.2:c.1183C>T (chr16-4575663-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145011.2(C16orf96):c.1183C>T(p.Leu395Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000684 in 1,535,916 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

C16orf96
NM_001145011.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.55

Publications

1 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015774071).

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.1183C>T	p.Leu395Phe	missense	Exon 5 of 16	NP_001138483.1	A6NNT2
	C16orf96	NM_001387219.1		c.1183C>T	p.Leu395Phe	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.1183C>T	p.Leu395Phe	missense	Exon 5 of 16	ENSP00000415027.3	A6NNT2

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000437

AC:

AN:

137430

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000846

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000361

AC:

AN:

1383584

Hom.:

Cov.:

AF XY:

0.0000308

AC XY:

AN XY:

681290

show subpopulations

African (AFR)

AF:

0.00128

AC:

AN:

31202

American (AMR)

AF:

0.00

AC:

AN:

33580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23840

East Asian (EAS)

AF:

0.00

AC:

AN:

35634

South Asian (SAS)

AF:

0.0000130

AC:

AN:

76902

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47428

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5494

European-Non Finnish (NFE)

AF:

0.00000280

AC:

AN:

1072278

Other (OTH)

AF:

0.000105

AC:

AN:

57226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000361

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00128

AC:

AN:

41562

American (AMR)

AF:

0.0000653

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000497

Hom.:

Bravo

AF:

0.000480

ExAC

AF:

0.0000765

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.67

CADD

Benign

6.2

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0041

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.41

M_CAP

Benign

0.0075

MetaRNN

Benign

0.016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

-1.6

PROVEAN

Benign

-0.98

REVEL

Benign

0.047

Sift

Pathogenic

0.0

Sift4G

Benign

0.11

Polyphen

0.92

Vest4

0.037

MVP

0.067

ClinPred

0.057

GERP RS

-1.9

Varity_R

0.098

gMVP

0.056

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

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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