1-59990830-A-G

Position:

• chr1-59990830-A-G

Variant summary

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

The NM_152377.3(C1orf87):​c.1484T>C​(p.Val495Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 0.0000082 (0 hom.)
• Consequence: C1orf87 NM_152377.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58

Genes affected

C1orf87 (HGNC:28547): (chromosome 1 open reading frame 87)

C1orf87 (HGNC:):

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=0.13068846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1orf87	NM_152377.3	c.1484T>C	p.Val495Ala	missense_variant	12/12	ENST00000371201.3	NP_689590.1
C1orf87	XM_017000307.2	c.1340T>C	p.Val447Ala	missense_variant	11/11		XP_016855796.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1orf87	ENST00000371201.3	c.1484T>C	p.Val495Ala	missense_variant	12/12	1	NM_152377.3	ENSP00000360244.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461552 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727062

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: 0.0000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jul 20, 2021

The c.1484T>C (p.V495A) alteration is located in exon 12 (coding exon 11) of the C1orf87 gene. This alteration results from a T to C substitution at nucleotide position 1484, causing the valine (V) at amino acid position 495 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	Benign	0.19
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.043	.;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.36	T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	.;M
PROVEAN	Benign	-1.9	.;N
REVEL	Benign	0.031
Sift	Benign	0.21	.;T
Sift4G	Uncertain	0.021	D;D
Polyphen		0.019	.;B
Vest4		0.23
MutPred		0.30		.;Gain of helix (P = 0.0199);
MVP		0.22
MPC		0.063
ClinPred		0.14	T
GERP RS		2.2
Varity_R		0.069
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-60456502;