Variant 11-83280143-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001286116.2(CCDC90B):c.-86A>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000041 in 1,609,742 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

CCDC90B
NM_001286116.2 5_prime_UTR_premature_start_codon_gain

Scores

Splicing: ADA: 0.9953

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.66

Variant links:

Genes affected

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

CCDC90B links:

CCDC90B (HGNC:):

CCDC90B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.218A>T	p.His73Leu	missense_variant, splice_region_variant	2/9	ENST00000529689.6	NP_068597.2	Q9GZT6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC90B	ENST00000529689.6 linkuse as main transcript	c.218A>T	p.His73Leu	missense_variant, splice_region_variant	2/9	1	NM_021825.5	ENSP00000434724.1		Q9GZT6-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

248744

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134502

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000219

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000439

AC:

AN:

1457518

Hom.:

Cov.:

AF XY:

0.0000414

AC XY:

AN XY:

725010

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00162

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000384

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2024

The c.218A>T (p.H73L) alteration is located in exon 2 (coding exon 2) of the CCDC90B gene. This alteration results from a A to T substitution at nucleotide position 218, causing the histidine (H) at amino acid position 73 to be replaced by a leucine (L). 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

0.16

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.059

T;.;.

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.53

T;T;T

M_CAP

Benign

0.0097

MetaRNN

Uncertain

0.49

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-4.9

D;D;D

REVEL

Benign

0.086

Sift

Benign

0.041

D;D;D

Sift4G

Benign

0.14

T;T;T

Polyphen

0.41

B;B;.

Vest4

0.56

MutPred

0.48

Loss of disorder (P = 0.0649);.;Loss of disorder (P = 0.0649);

MVP

0.58

MPC

0.11

ClinPred

0.68

GERP RS

5.6

Varity_R

0.69

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.73

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over