16-4575541-C-G

Variant names:

• chr16-4575541-C-G
• rs1046739166
• NM_001145011.2:c.1061C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145011.2(C16orf96):​c.1061C>G​(p.Pro354Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 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. P354L) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 33)
• Consequence: C16orf96 NM_001145011.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.78
• Publications: 1 publications found

Genes affected

C16orf96 (HGNC:40031): (chromosome 16 open reading frame 96)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.064477414).

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.1061C>G	p.Pro354Arg	missense	Exon 5 of 16	NP_001138483.1	A6NNT2
	C16orf96	NM_001387219.1		c.1061C>G	p.Pro354Arg	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.1061C>G	p.Pro354Arg	missense	Exon 5 of 16	ENSP00000415027.3	A6NNT2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152206 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 36

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152206 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74366

African (AFR) AF: 0.0000482 AC: 2 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.0090
DANN	Benign	0.81
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0072	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-4.8
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.14
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.065	T
Polyphen		0.36	B
Vest4		0.058
MutPred		0.35		Gain of methylation at P354 (P = 0.029)
MVP		0.067
ClinPred		0.087	T
GERP RS		-6.2
Varity_R		0.070
gMVP		0.15

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: rs1046739166; hg19: chr16-4625542;