chr20-278354-C-T

Variant names:

• chr20-278354-C-T
• NM_153269.3:c.541G>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.541G>A​(p.Glu181Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,696 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: C20orf96 NM_153269.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0420
• 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=0.1166434).

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.541G>A	p.Glu181Lys	missense	Exon 6 of 11	NP_695001.2	Q9NUD7
	C20orf96	NM_080571.2		c.538G>A	p.Glu180Lys	missense	Exon 6 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.541G>A	p.Glu181Lys	missense	Exon 6 of 11	ENSP00000353470.2	Q9NUD7
	C20orf96	ENST00000400269.4	TSL:1	c.538G>A	p.Glu180Lys	missense	Exon 6 of 11	ENSP00000383128.4	F5GZA9
	C20orf96	ENST00000907056.1		c.541G>A	p.Glu181Lys	missense	Exon 6 of 10	ENSP00000577115.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461696 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727148

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

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

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111852

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 31

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	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.066	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.042
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.051
Sift	Benign	0.25	T
Sift4G	Uncertain	0.026	D
Polyphen		0.69	P
Vest4		0.38
MutPred		0.35		Gain of MoRF binding (P = 0.0021)
MVP		0.48
MPC		0.099
ClinPred		0.43	T
GERP RS		1.9
Varity_R		0.059
gMVP		0.11
Mutation Taster		=96/4	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

hg19: chr20-258995; COSMIC: COSV100826687;