16-27067006-C-T

Position:

• chr16-27067006-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.00

Genes affected

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

(HGNC:):

ACMG classification

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 (BayesDel_noAF=-0.49).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C16orf82	NM_001145545.2	c.11C>T	p.Pro4Leu	missense_variant	1/1	ENST00000505035.3	NP_001139017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C16orf82	ENST00000505035.3	c.11C>T	p.Pro4Leu	missense_variant	1/1		NM_001145545.2	ENSP00000500329	P1
	ENST00000565783.1	n.438-17G>A		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.000749 AC: 114 AN: 152216 Hom.: 0 Cov.: 32

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

GnomAD3 exomes AF: 0.000747 AC: 186 AN: 249044 Hom.: 0 AF XY: 0.000807 AC XY: 109 AN XY: 135128

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 SAS exome AF: 0.00111

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.: 0 Cov.: 30 AF XY: 0.00110 AC XY: 660 AN XY: 602322

Gnomad4 AFR exome AF: 0.000380

Gnomad4 AMR exome AF: 0.000268

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00119

Gnomad4 FIN exome AF: 0.0000615

Gnomad4 NFE exome AF: 0.00124

Gnomad4 OTH exome AF: 0.000636

GnomAD4 genome AF: 0.000742 AC: 113 AN: 152334 Hom.: 0 Cov.: 32 AF XY: 0.000806 AC XY: 60 AN XY: 74480

Gnomad4 AFR AF: 0.000240

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00132

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00103 Hom.: 2

Bravo AF: 0.000559

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

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	23
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs200270667; hg19: chr16-27078327;