Variant 12-28484157-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018318.5(CCDC91):c.1207C>A(p.Gln403Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00303 in 1,587,890 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 71 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 64 hom. )

Consequence

CCDC91
NM_018318.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.52

Variant links:

Genes affected

CCDC91 (HGNC:24855): (coiled-coil domain containing 91) Predicted to enable identical protein binding activity. Involved in Golgi to lysosome transport. Located in nucleoplasm and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

CCDC91 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002758503).

BP6

Variant 12-28484157-C-A is Benign according to our data. Variant chr12-28484157-C-A is described in ClinVar as [Benign]. Clinvar id is 781069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC91	NM_018318.5 linkuse as main transcript	c.1207C>A	p.Gln403Lys	missense_variant	12/13	ENST00000536442.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC91	ENST00000536442.6 linkuse as main transcript	c.1207C>A	p.Gln403Lys	missense_variant	12/13	5	NM_018318.5	P1	Q7Z6B0-1

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2484

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0564

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00748

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00399

AC:

933

AN:

233624

Hom.:

AF XY:

0.00302

AC XY:

379

AN XY:

125532

show subpopulations

Gnomad AFR exome

AF:

0.0561

Gnomad AMR exome

AF:

0.00264

Gnomad ASJ exome

AF:

0.000104

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000717

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00139

GnomAD4 exome

AF:

0.00162

AC:

2332

AN:

1435750

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

1033

AN XY:

714018

show subpopulations

Gnomad4 AFR exome

AF:

0.0586

Gnomad4 AMR exome

AF:

0.00296

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000478

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000503

Gnomad4 OTH exome

AF:

0.00360

GnomAD4 genome

AF:

0.0163

AC:

2485

AN:

152140

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1173

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0563

Gnomad4 AMR

AF:

0.00747

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00111

Hom.:

Bravo

AF:

0.0187

ESP6500AA

AF:

0.0538

AC:

237

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00487

AC:

591

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.032

.;T;T;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.89

D;.;D;D

MetaRNN

Benign

0.0028

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

.;N;N;.

MutationTaster

Benign

0.58

N;N;N;N;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.4

N;N;N;N

REVEL

Benign

0.23

Sift

Benign

0.30

T;T;T;D

Sift4G

Benign

0.14

T;T;T;T

Polyphen

0.95

P;P;P;.

Vest4

0.79

MVP

0.55

MPC

0.49

ClinPred

0.021

GERP RS

5.7

Varity_R

0.20

gMVP

0.30

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

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