chr1-197902678-C-A

Position:

• chr1-197902678-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000367393.8(C1orf53):​c.29C>A​(p.Thr10Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 1,343,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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: 0.000013 (0 hom.)
• Consequence: C1orf53 ENST00000367393.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.139

Genes affected

C1orf53 (HGNC:30003): (chromosome 1 open reading frame 53)

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=0.06332132).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1orf53	NM_001024594.3	c.29C>A	p.Thr10Lys	missense_variant	1/3	ENST00000367393.8	NP_001019765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1orf53	ENST00000367393.8	c.29C>A	p.Thr10Lys	missense_variant	1/3	1	NM_001024594.3	ENSP00000356363	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000134 AC: 18 AN: 1343318 Hom.: 0 Cov.: 31 AF XY: 0.0000106 AC XY: 7 AN XY: 663082

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000572

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000178

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

Sep 16, 2021

The c.29C>A (p.T10K) alteration is located in exon 1 (coding exon 1) of the C1orf53 gene. This alteration results from a C to A substitution at nucleotide position 29, causing the threonine (T) at amino acid position 10 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	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	13
DANN	Benign	0.89
DEOGEN2	Benign	0.0074	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PROVEAN	Benign	0.050	N
REVEL	Benign	0.015
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.17	T
Polyphen		0.0010	B
Vest4		0.21
MutPred		0.31		Gain of glycosylation at T10 (P = 0.0448);
MVP		0.030
MPC		0.23
ClinPred		0.15	T
GERP RS		0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.069
gMVP		0.21

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

LitVar

Other links and lift over

dbSNP: rs1297385438; hg19: chr1-197871808;