rs1030353364

Variant names:

• chr11-83273852-G-C
• rs1030353364
• NM_021825.5:c.481C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-83273852-G-C
• chr11-83273852-G-A
• chr11-83273852-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R161Q) has been classified as Uncertain significance.

• 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
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021825.5. 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
	CCDC90B	NM_021825.5	MANE Select	c.481C>G	p.Arg161Gly	missense	Exon 6 of 9	NP_068597.2
	CCDC90B	NM_001286118.3		c.187C>G	p.Arg63Gly	missense	Exon 5 of 8	NP_001273047.1
	CCDC90B	NM_001286119.3		c.187C>G	p.Arg63Gly	missense	Exon 6 of 9	NP_001273048.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC90B	ENST00000529689.6	TSL:1 MANE Select	c.481C>G	p.Arg161Gly	missense	Exon 6 of 9	ENSP00000434724.1	Q9GZT6-1
	CCDC90B	ENST00000455220.6	TSL:1	c.178C>G	p.Arg60Gly	missense	Exon 6 of 9	ENSP00000390990.3	Q9GZT6-3
	CCDC90B	ENST00000525503.5	TSL:1	n.*669C>G		non_coding_transcript_exon	Exon 6 of 9	ENSP00000431424.2	E9PSG6

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

African (AFR) AF: 0.00 AC: 0 AN: 33264

American (AMR) AF: 0.00 AC: 0 AN: 44112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25928

East Asian (EAS) AF: 0.00 AC: 0 AN: 39472

South Asian (SAS) AF: 0.00 AC: 0 AN: 85270

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1108964

Other (OTH) AF: 0.00 AC: 0 AN: 60128

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	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
Eigen	Benign	-0.041
Eigen_PC	Benign	-0.00052
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.2
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.64	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
Mutation Taster		=84/16	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: rs1030353364; hg19: chr11-82984895;