NM_152337.3:c.638C>G

Variant names:

• chr16-81061711-G-C
• rs138763234
• NM_152337.3:c.638C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152337.3(C16orf46):​c.638C>G​(p.Pro213Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,740 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P213L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: C16orf46 NM_152337.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.12
• Publications: 3 publications found

Genes affected

C16orf46 (HGNC:26525): (chromosome 16 open reading frame 46) Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000284512 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152337.3. 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
	C16orf46	NM_152337.3	MANE Select	c.638C>G	p.Pro213Arg	missense	Exon 4 of 4	NP_689550.2	Q6P387-1
	C16orf46	NM_001100873.2		c.638C>G	p.Pro213Arg	missense	Exon 3 of 4	NP_001094343.1	Q6P387-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C16orf46	ENST00000299578.10	TSL:2 MANE Select	c.638C>G	p.Pro213Arg	missense	Exon 4 of 4	ENSP00000299578.4	Q6P387-1
	C16orf46	ENST00000378611.8	TSL:1	c.638C>G	p.Pro213Arg	missense	Exon 3 of 4	ENSP00000367874.4	Q6P387-2
	ENSG00000284512	ENST00000640345.1	TSL:5	c.424+22752C>G		intron	N/A	ENSP00000492798.1	A0A1W2PS29

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251094 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

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: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461740 Hom.: 0 Cov.: 85 AF XY: 0.00000138 AC XY: 1 AN XY: 727180

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

Alfa AF: 0.00000386 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.1
PROVEAN	Pathogenic	-9.0	D
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.73
MutPred		0.43		Gain of MoRF binding (P = 0.0041)
MVP		0.39
MPC		0.10
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.65
gMVP		0.34

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

Other links and lift over

dbSNP: rs138763234; hg19: chr16-81095316;