chr20-33663844-C-G

Position:

• chr20-33663844-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080825.4(C20orf144):​c.439C>G​(p.Arg147Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000797 in 1,254,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: C20orf144 NM_080825.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.476

Genes affected

C20orf144 (HGNC:16137): (chromosome 20 open reading frame 144)

NECAB3 (HGNC:15851): (N-terminal EF-hand calcium binding protein 3) The protein encoded by this gene interacts with the amino-terminal domain of the neuron-specific X11-like protein (X11L), inhibits the association of X11L with amyloid precursor protein through a non-competitive mechanism, and abolishes the suppression of beta-amyloid production by X11L. This protein, together with X11L, may play an important role in the regulatory system of amyloid precursor protein metabolism and beta-amyloid generation. The protein is phosphorylated by NIMA-related expressed kinase 2, and localizes to the Golgi apparatus. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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=0.22055447).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C20orf144	NM_080825.4	c.439C>G	p.Arg147Gly	missense_variant	2/2	ENST00000375222.4	NP_543015.1
NECAB3	NM_031232.4	c.388-3449G>C		intron_variant		ENST00000246190.11	NP_112509.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C20orf144	ENST00000375222.4	c.439C>G	p.Arg147Gly	missense_variant	2/2	1	NM_080825.4	ENSP00000364370.3
NECAB3	ENST00000246190.11	c.388-3449G>C		intron_variant		5	NM_031232.4	ENSP00000246190.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.97e-7 AC: 1 AN: 1254824 Hom.: 0 Cov.: 31 AF XY: 0.00000164 AC XY: 1 AN XY: 611486

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: 9.77e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Oct 29, 2021

The c.439C>G (p.R147G) alteration is located in exon 2 (coding exon 2) of the C20orf144 gene. This alteration results from a C to G substitution at nucleotide position 439, causing the arginine (R) at amino acid position 147 to be replaced by a glycine (G). 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	0.17
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	13
DANN	Benign	0.73
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.30	T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.10
Sift	Benign	0.11	T
Sift4G	Uncertain	0.029	D
Polyphen		0.88	P
Vest4		0.32
MutPred		0.14		Loss of MoRF binding (P = 0.0032);
MVP		0.47
MPC		0.95
ClinPred		0.39	T
GERP RS		2.8
Varity_R		0.16
gMVP		0.043

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: chr20-32251650;