rs1058636

Positions:

• chr16-67667981-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001012984.3(C16orf86):​c.436C>G​(p.Pro146Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: C16orf86 NM_001012984.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758

Genes affected

C16orf86 (HGNC:33755): (chromosome 16 open reading frame 86)

C16orf86 (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 (MetaRNN=0.051833063).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C16orf86	NM_001012984.3	c.436C>G	p.Pro146Ala	missense_variant	3/4	ENST00000403458.9	NP_001013002.2
C16orf86	XM_047434097.1	c.481C>G	p.Pro161Ala	missense_variant	1/2		XP_047290053.1
C16orf86	XM_047434098.1	c.481C>G	p.Pro161Ala	missense_variant	1/2		XP_047290054.1
C16orf86	XM_005255952.6	c.436C>G	p.Pro146Ala	missense_variant	3/4		XP_005256009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C16orf86	ENST00000403458.9	c.436C>G	p.Pro146Ala	missense_variant	3/4	1	NM_001012984.3	ENSP00000384117.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	2.4
DANN	Benign	0.68
DEOGEN2	Benign	0.20	T;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.54	T;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.052	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;.;.
PROVEAN	Pathogenic	-5.3	D;.;.
REVEL	Benign	0.089
Sift	Benign	0.069	T;.;.
Sift4G	Benign	0.73	T;T;T
Polyphen		0.073	B;.;.
Vest4		0.18
MutPred		0.099		Loss of glycosylation at P146 (P = 0.0376);Loss of glycosylation at P146 (P = 0.0376);.;
MVP		0.043
MPC		0.39
ClinPred		0.061	T
GERP RS		1.1
Varity_R		0.068
gMVP		0.037

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

Other links and lift over

dbSNP: rs1058636; hg19: chr16-67701884;