20-278354-C-T

Position:

• chr20-278354-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/20 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

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1166434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C20orf96	NM_153269.3	c.541G>A	p.Glu181Lys	missense_variant	6/11	ENST00000360321.7	NP_695001.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C20orf96	ENST00000360321.7	c.541G>A	p.Glu181Lys	missense_variant	6/11	1	NM_153269.3	ENSP00000353470.2
C20orf96	ENST00000400269.4	c.538G>A	p.Glu180Lys	missense_variant	6/11	1		ENSP00000383128.4
C20orf96	ENST00000382369.9	c.436G>A	p.Glu146Lys	missense_variant	4/9	5		ENSP00000371806.5

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.541G>A (p.E181K) alteration is located in exon 6 (coding exon 6) of the C20orf96 gene. This alteration results from a G to A substitution at nucleotide position 541, causing the glutamic acid (E) at amino acid position 181 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	.;L;.
PROVEAN	Benign	-2.1	N;N;.
REVEL	Benign	0.051
Sift	Benign	0.25	T;T;.
Sift4G	Uncertain	0.026	D;D;D
Polyphen		0.69	P;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-258995; COSMIC: COSV100826687;