16-4575663-C-G

Variant names:

• chr16-4575663-C-G
• rs577103751
• NM_001145011.2:c.1183C>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.1183C>G​(p.Leu395Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000506 in 1,383,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. L395F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000051 (0 hom.)
• Consequence: C16orf96 NM_001145011.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 0 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=0.04679656).

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.1183C>G	p.Leu395Val	missense	Exon 5 of 16	NP_001138483.1	A6NNT2
	C16orf96	NM_001387219.1		c.1183C>G	p.Leu395Val	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.1183C>G	p.Leu395Val	missense	Exon 5 of 16	ENSP00000415027.3	A6NNT2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000506 AC: 7 AN: 1383584 Hom.: 0 Cov.: 36 AF XY: 0.00000587 AC XY: 4 AN XY: 681290

African (AFR) AF: 0.00 AC: 0 AN: 31202

American (AMR) AF: 0.00 AC: 0 AN: 33580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23840

East Asian (EAS) AF: 0.00 AC: 0 AN: 35634

South Asian (SAS) AF: 0.00 AC: 0 AN: 76902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47428

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5494

European-Non Finnish (NFE) AF: 0.00000653 AC: 7 AN: 1072278

Other (OTH) AF: 0.00 AC: 0 AN: 57226

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.0
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0050	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-1.6
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.0070
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.12	T
Polyphen		0.0090	B
Vest4		0.016
MutPred		0.21		Gain of MoRF binding (P = 0.0849)
MVP		0.099
ClinPred		0.063	T
GERP RS		-1.9
Varity_R		0.069
gMVP		0.044
Mutation Taster		=98/2	polymorphism

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: rs577103751; hg19: chr16-4625664;