Genetic Variant C16orf82:p.Pro4Leu (chr16-27067006-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_001145545.2(C16orf82):c.11C>T(p.Pro4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,367,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

C16orf82
NM_001145545.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.00

Publications

2 publications found

Variant links:

Genes affected

C16orf82 (HGNC:30755): (chromosome 16 open reading frame 82)

C16orf82 links:

ENSG00000261482 (HGNC:):

ENSG00000261482 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 (BayesDel_noAF=-0.49).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C16orf82	NM_001145545.2 link	c.11C>T	p.Pro4Leu	missense_variant	Exon 1 of 1	ENST00000505035.3	NP_001139017.1	Q7Z2V1A0A5F9ZHF3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C16orf82	ENST00000505035.3 link	c.11C>T	p.Pro4Leu	missense_variant	Exon 1 of 1	6	NM_001145545.2	ENSP00000500329.2		A0A5F9ZHF3

Frequencies

GnomAD3 genomes

AF:

0.000749

AC:

114

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000747

AC:

186

AN:

249044

AF XY:

0.000807

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.00110

AC:

1333

AN:

1215366

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

660

AN XY:

602322

show subpopulations

African (AFR)

AF:

0.000380

AC:

AN:

26300

American (AMR)

AF:

0.000268

AC:

AN:

37288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16896

East Asian (EAS)

AF:

0.00

AC:

AN:

16806

South Asian (SAS)

AF:

0.00119

AC:

AN:

83226

European-Finnish (FIN)

AF:

0.0000615

AC:

AN:

32544

Middle Eastern (MID)

AF:

0.000894

AC:

AN:

4474

European-Non Finnish (NFE)

AF:

0.00124

AC:

1180

AN:

953828

Other (OTH)

AF:

0.000636

AC:

AN:

44004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

154

232

309

386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000742

AC:

113

AN:

152334

Hom.:

Cov.:

AF XY:

0.000806

AC XY:

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000240

AC:

AN:

41580

American (AMR)

AF:

0.000327

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00104

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00132

AC:

AN:

68032

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000983

Hom.:

Bravo

AF:

0.000559

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 11, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.11C>T (p.P4L) alteration is located in exon 1 (coding exon 1) of the C16orf82 gene. This alteration results from a C to T substitution at nucleotide position 11, causing the proline (P) at amino acid position 4 to be replaced by a leucine (L). 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

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

1.0

PromoterAI

0.0038

Neutral

(source)

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr16-27067006-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over