20-279210-G-T

Position:

• chr20-279210-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_153269.3(C20orf96):​c.427C>A​(p.His143Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C20orf96 NM_153269.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.156

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07525769).
• BP6: Variant 20-279210-G-T is Benign according to our data. Variant chr20-279210-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2259571.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C20orf96	NM_153269.3	c.427C>A	p.His143Asn	missense_variant	5/11	ENST00000360321.7	NP_695001.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C20orf96	ENST00000360321.7	c.427C>A	p.His143Asn	missense_variant	5/11	1	NM_153269.3	ENSP00000353470.2
C20orf96	ENST00000400269.4	c.424C>A	p.His142Asn	missense_variant	5/11	1		ENSP00000383128.4
C20orf96	ENST00000382369.9	c.322C>A	p.His108Asn	missense_variant	3/9	5		ENSP00000371806.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1456480 Hom.: 0 Cov.: 45 AF XY: 0.00 AC XY: 0 AN XY: 724856

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.1
DANN	Benign	0.67
DEOGEN2	Benign	0.019	.;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0058	N
LIST_S2	Benign	0.16	T;T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.075	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.2	.;N;.
PROVEAN	Benign	0.73	N;N;.
REVEL	Benign	0.047
Sift	Benign	0.47	T;T;.
Sift4G	Benign	0.43	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.20
MutPred		0.12		.;Gain of disorder (P = 0.0665);.;
MVP		0.15
MPC		0.049
ClinPred		0.075	T
GERP RS		0.94
Varity_R		0.053
gMVP		0.079

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: chr20-259851;