20-279213-G-T

Variant names:

• chr20-279213-G-T
• rs199683042
• NM_153269.3:c.424C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153269.3(C20orf96):​c.424C>A​(p.Leu142Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. L142V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: C20orf96 NM_153269.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.981
• Publications: 0 publications found

Genes affected

C20orf96 (HGNC:16227): (chromosome 20 open reading frame 96)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09828538).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153269.3. 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
	C20orf96	NM_153269.3	MANE Select	c.424C>A	p.Leu142Met	missense	Exon 5 of 11	NP_695001.2	Q9NUD7
	C20orf96	NM_080571.2		c.421C>A	p.Leu141Met	missense	Exon 5 of 11	NP_542138.1	F5GZA9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C20orf96	ENST00000360321.7	TSL:1 MANE Select	c.424C>A	p.Leu142Met	missense	Exon 5 of 11	ENSP00000353470.2	Q9NUD7
	C20orf96	ENST00000400269.4	TSL:1	c.421C>A	p.Leu141Met	missense	Exon 5 of 11	ENSP00000383128.4	F5GZA9
	C20orf96	ENST00000907056.1		c.424C>A	p.Leu142Met	missense	Exon 5 of 10	ENSP00000577115.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457250 Hom.: 0 Cov.: 45 AF XY: 0.00 AC XY: 0 AN XY: 725258

African (AFR) AF: 0.00 AC: 0 AN: 33228

American (AMR) AF: 0.00 AC: 0 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25998

East Asian (EAS) AF: 0.00 AC: 0 AN: 39476

South Asian (SAS) AF: 0.00 AC: 0 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110918

Other (OTH) AF: 0.00 AC: 0 AN: 60248

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.0
DANN	Benign	0.96
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.98
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.026
Sift	Benign	0.20	T
Sift4G	Benign	0.18	T
Polyphen		0.80	P
Vest4		0.28
MutPred		0.23		Gain of disorder (P = 0.0927)
MVP		0.17
MPC		0.15
ClinPred		0.22	T
GERP RS		-1.1
Varity_R		0.054
gMVP		0.049
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: rs199683042; hg19: chr20-259854;