chr1-1087514-C-T

Variant names:

• chr1-1087514-C-T
• rs374125094
• NM_017891.5:c.232G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017891.5(C1orf159):​c.232G>A​(p.Glu78Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,397,180 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000093 (0 hom.)
• Consequence: C1orf159 NM_017891.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.752
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14773777).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017891.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf159	NM_017891.5	MANE Select	c.232G>A	p.Glu78Lys	missense	Exon 5 of 10	NP_060361.4
	C1orf159	NM_001330306.2		c.340G>A	p.Glu114Lys	missense	Exon 7 of 12	NP_001317235.1	Q96HA4-1
	C1orf159	NM_001363525.2		c.232G>A	p.Glu78Lys	missense	Exon 6 of 11	NP_001350454.1	Q5T2W9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf159	ENST00000421241.7	TSL:2 MANE Select	c.232G>A	p.Glu78Lys	missense	Exon 5 of 10	ENSP00000400736.2	Q96HA4-4
	C1orf159	ENST00000379339.5	TSL:2	c.340G>A	p.Glu114Lys	missense	Exon 7 of 12	ENSP00000368644.1	Q96HA4-1
	C1orf159	ENST00000379320.5	TSL:2	c.232G>A	p.Glu78Lys	missense	Exon 3 of 8	ENSP00000368624.1	Q5T2W9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000655 AC: 1 AN: 152618 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000674

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000930 AC: 13 AN: 1397180 Hom.: 0 Cov.: 31 AF XY: 0.00000726 AC XY: 5 AN XY: 688998

African (AFR) AF: 0.00 AC: 0 AN: 31588

American (AMR) AF: 0.00 AC: 0 AN: 35646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25146

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35716

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79216

European-Finnish (FIN) AF: 0.0000209 AC: 1 AN: 47862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00000835 AC: 9 AN: 1078376

Other (OTH) AF: 0.00 AC: 0 AN: 57940

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000314 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	20
DANN	Benign	0.83
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.75
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.11
Sift	Benign	0.043	D
Sift4G	Benign	0.77	T
Polyphen		0.93	P
Vest4		0.25
MVP		0.37
MPC		0.097
ClinPred		0.10	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.61
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs374125094; hg19: chr1-1022894;