11-83278800-C-A

Variant names:

• chr11-83278800-C-A
• rs373524286
• NM_021825.5:c.250G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_021825.5(CCDC90B):​c.250G>T​(p.Val84Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC90B NM_021825.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.57
• Publications: 1 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.824

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.250G>T	p.Val84Leu	missense	Exon 3 of 9	NP_068597.2
	CCDC90B	NM_001286116.2		c.-54G>T		5_prime_UTR	Exon 3 of 9	NP_001273045.2	Q9GZT6-3
	CCDC90B	NM_001286117.3		c.-54G>T		5_prime_UTR	Exon 3 of 9	NP_001273046.1	Q9GZT6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC90B	ENST00000529689.6	TSL:1 MANE Select	c.250G>T	p.Val84Leu	missense	Exon 3 of 9	ENSP00000434724.1	Q9GZT6-1
	CCDC90B	ENST00000455220.6	TSL:1	c.-54G>T		5_prime_UTR	Exon 3 of 9	ENSP00000390990.3	Q9GZT6-3
	CCDC90B	ENST00000525503.5	TSL:1	n.*438G>T		non_coding_transcript_exon	Exon 3 of 9	ENSP00000431424.2	E9PSG6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251298 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.55	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		4.6
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.27
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.95	P
Vest4		0.74
MutPred		0.81		Gain of disorder (P = 0.2202)
MVP		0.73
MPC		0.055
ClinPred		0.97	D
GERP RS		5.5
PromoterAI		-0.025	Neutral
Varity_R		0.86
gMVP		0.71
Mutation Taster		=22/78	disease causing

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

Other links and lift over

dbSNP: rs373524286; hg19: chr11-82989843;