11-83280146-G-A

Variant names:

• chr11-83280146-G-A
• rs1382921691
• NM_021825.5:c.215C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021825.5(CCDC90B):​c.215C>T​(p.Thr72Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000046 in 1,457,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: CCDC90B NM_021825.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.95

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29721147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC90B	NM_021825.5	c.215C>T	p.Thr72Ile	missense_variant	Exon 2 of 9	ENST00000529689.6	NP_068597.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC90B	ENST00000529689.6	c.215C>T	p.Thr72Ile	missense_variant	Exon 2 of 9	1	NM_021825.5	ENSP00000434724.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248914 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134638

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000460 AC: 67 AN: 1457848 Hom.: 0 Cov.: 30 AF XY: 0.0000455 AC XY: 33 AN XY: 725194

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: 0.0000603

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

Feb 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.215C>T (p.T72I) alteration is located in exon 2 (coding exon 2) of the CCDC90B gene. This alteration results from a C to T substitution at nucleotide position 215, causing the threonine (T) at amino acid position 72 to be replaced by an isoleucine (I). 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	0.11
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T;.;.
Eigen	Benign	0.18
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.85	T
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Benign	0.070
Sift	Benign	0.14	T;T;D
Sift4G	Benign	0.096	T;T;T
Polyphen		0.84	P;P;.
Vest4		0.41
MutPred		0.33		Loss of disorder (P = 0.0418);.;Loss of disorder (P = 0.0418);
MVP		0.63
MPC		0.052
ClinPred		0.52	D
GERP RS		2.6
Varity_R		0.24
gMVP		0.32

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: rs1382921691; hg19: chr11-82991189;