11-83273852-G-C

Position:

• chr11-83273852-G-C

Variant summary

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

The NM_021825.5(CCDC90B):​c.481C>G​(p.Arg161Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,455,980 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: CCDC90B NM_021825.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.25

Genes affected

CCDC90B (HGNC:28108): (coiled-coil domain containing 90B) Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

CCDC90B (HGNC:):

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/exons	MANE	Protein	UniProt
CCDC90B	NM_021825.5	c.481C>G	p.Arg161Gly	missense_variant	6/9	ENST00000529689.6	NP_068597.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC90B	ENST00000529689.6	c.481C>G	p.Arg161Gly	missense_variant	6/9	1	NM_021825.5	ENSP00000434724.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1455980 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 724008

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: 0.0000135

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Nov 13, 2024

The c.481C>G (p.R161G) alteration is located in exon 6 (coding exon 6) of the CCDC90B gene. This alteration results from a C to G substitution at nucleotide position 481, causing the arginine (R) at amino acid position 161 to be replaced by a glycine (G). 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	0.21
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T;.;.;.;T
Eigen	Benign	-0.041
Eigen_PC	Benign	-0.00052
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D;D;.;D;D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.45	T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.8	L;.;.;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-4.1	D;D;D;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D
Polyphen		0.64	P;P;.;.;.
Vest4		0.49
MutPred		0.64		Loss of MoRF binding (P = 0.028);.;.;.;.;
MVP		0.57
MPC		0.14
ClinPred		0.99	D
GERP RS		1.8
Varity_R		0.64
gMVP		0.53

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

LitVar

Other links and lift over

dbSNP: rs1030353364; hg19: chr11-82984895;