rs1896943668

Variant names:

• chr16-4587055-T-A
• rs1896943668
• NM_001145011.2:c.2369T>A

Variant summary

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

The NM_001145011.2(C16orf96):​c.2369T>A​(p.Ile790Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,399,240 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: C16orf96 NM_001145011.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.91
• Publications: 0 publications found

Genes affected

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

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_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.2369T>A	p.Ile790Asn	missense	Exon 8 of 16	NP_001138483.1	A6NNT2
	C16orf96	NM_001387219.1		c.2369T>A	p.Ile790Asn	missense	Exon 10 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.2369T>A	p.Ile790Asn	missense	Exon 8 of 16	ENSP00000415027.3	A6NNT2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399240 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 690108

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000633 AC: 2 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25174

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.00 AC: 0 AN: 79228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078902

Other (OTH) AF: 0.00 AC: 0 AN: 57996

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.035
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.9
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.21
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.49		Gain of disorder (P = 0.0399)
MVP		0.16
ClinPred		0.97	D
GERP RS		5.2
Varity_R		0.60
gMVP		0.28
Mutation Taster		=97/3	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: rs1896943668; hg19: chr16-4637056;