1-1090403-T-G

Position:

• chr1-1090403-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017891.5(C1orf159):​c.98A>C​(p.Asp33Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: C1orf159 NM_017891.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.07

Genes affected

C1orf159 (HGNC:26062): (chromosome 1 open reading frame 159) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37597767).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1orf159	NM_017891.5	c.98A>C	p.Asp33Ala	missense_variant	4/10	ENST00000421241.7	NP_060361.4
C1orf159	NM_001330306.2	c.206A>C	p.Asp69Ala	missense_variant	6/12		NP_001317235.1
C1orf159	NM_001363525.2	c.98A>C	p.Asp33Ala	missense_variant	5/11		NP_001350454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1orf159	ENST00000421241.7	c.98A>C	p.Asp33Ala	missense_variant	4/10	2	NM_017891.5	ENSP00000400736	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398200 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689624

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

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

Aug 02, 2021

The c.98A>C (p.D33A) alteration is located in exon 4 (coding exon 2) of the C1orf159 gene. This alteration results from a A to C substitution at nucleotide position 98, causing the aspartic acid (D) at amino acid position 33 to be replaced by an alanine (A). 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	Uncertain	0.54
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;.;.;.;T;T;.;.
Eigen	Benign	0.18
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.71	T;.;T;T;T;T;T;T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.38	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.6	M;.;.;.;.;.;.;.
MutationTaster	Benign	0.73	D;D;D;D;D;D;D
PROVEAN	Pathogenic	-4.6	D;D;D;D;D;.;.;D
REVEL	Benign	0.17
Sift	Uncertain	0.0050	D;D;D;D;D;.;.;D
Sift4G	Uncertain	0.014	D;D;D;D;.;.;.;D
Polyphen		1.0	D;P;D;P;P;.;.;.
Vest4		0.23
MutPred		0.64		Gain of sheet (P = 0.0477);.;.;.;.;.;.;.;
MVP		0.31
MPC		0.21
ClinPred		0.99	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1645909709; hg19: chr1-1025783;