1-231229155-C-T

Variant names:

• chr1-231229155-C-T
• rs910714016
• NM_152379.4:c.505G>A

Variant summary

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

The NM_152379.4(C1orf131):​c.505G>A​(p.Glu169Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C1orf131 NM_152379.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.10

Genes affected

C1orf131 (HGNC:25332): (chromosome 1 open reading frame 131) Enables RNA binding activity. Located in chromosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1orf131	NM_152379.4	c.505G>A	p.Glu169Lys	missense_variant	Exon 3 of 7	ENST00000366649.7	NP_689592.2
C1orf131	NM_001300830.2	c.502G>A	p.Glu168Lys	missense_variant	Exon 3 of 7		NP_001287759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1orf131	ENST00000366649.7	c.505G>A	p.Glu169Lys	missense_variant	Exon 3 of 7	1	NM_152379.4	ENSP00000355609.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000416 AC: 1 AN: 240410 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 130206

Gnomad AFR exome AF: 0.0000638

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1406120 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 699728

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.: 33

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 14, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.505G>A (p.E169K) alteration is located in exon 3 (coding exon 3) of the C1orf131 gene. This alteration results from a G to A substitution at nucleotide position 505, causing the glutamic acid (E) at amino acid position 169 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	Pathogenic	0.75
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0057	T;T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.7	M;.;.
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.21
Sift	Benign	0.14	T;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.54
MutPred		0.71		Gain of MoRF binding (P = 0.0056);Gain of MoRF binding (P = 0.0056);.;
MVP		0.64
MPC		0.39
ClinPred		0.90	D
GERP RS		4.3
Varity_R		0.21
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs910714016; hg19: chr1-231364901;