10-122938125-A-G

Position:

• chr10-122938125-A-G

Variant summary

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

The NM_024942.4(C10orf88):​c.683T>C​(p.Val228Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: C10orf88 NM_024942.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.00

Genes affected

C10orf88 (HGNC:25822): (chromosome 10 open reading frame 88) Predicted to enable identical protein binding activity. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

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=0.12613541).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C10orf88	NM_024942.4	c.683T>C	p.Val228Ala	missense_variant	5/6	ENST00000481909.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C10orf88	ENST00000481909.2	c.683T>C	p.Val228Ala	missense_variant	5/6	1	NM_024942.4	P1
C10orf88	ENST00000368891.9	n.812T>C		non_coding_transcript_exon_variant	5/6	2
C10orf88	ENST00000470158.1	n.196T>C		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455930 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 723710

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: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

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

May 20, 2024

The c.683T>C (p.V228A) alteration is located in exon 5 (coding exon 5) of the C10orf88 gene. This alteration results from a T to C substitution at nucleotide position 683, causing the valine (V) at amino acid position 228 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	0.20
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	1.0	N
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.069
Sift	Benign	0.040	D
Sift4G	Benign	0.076	T
Polyphen		0.40	B
Vest4		0.16
MutPred		0.20		Loss of stability (P = 0.0557);
MVP		0.15
MPC		0.23
ClinPred		0.27	T
GERP RS		4.1
Varity_R		0.077
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-124697641;