Variant 12-28452517-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018318.5(CCDC91):c.964G>A(p.Val322Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000542 in 1,585,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

CCDC91
NM_018318.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.986

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02405107).

BP6

Variant 12-28452517-G-A is Benign according to our data. Variant chr12-28452517-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2204992.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC91	NM_018318.5 linkuse as main transcript	c.964G>A	p.Val322Ile	missense_variant	11/13	ENST00000536442.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC91	ENST00000536442.6 linkuse as main transcript	c.964G>A	p.Val322Ile	missense_variant	11/13	5	NM_018318.5	P1	Q7Z6B0-1

Frequencies

GnomAD3 genomes

AF:

0.0000924

AC:

AN:

151490

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000591

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.000102

AC:

AN:

234850

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

127614

show subpopulations

Gnomad AFR exome

AF:

0.000198

Gnomad AMR exome

AF:

0.000295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000647

Gnomad OTH exome

AF:

0.000354

GnomAD4 exome

AF:

0.0000502

AC:

AN:

1433774

Hom.:

Cov.:

AF XY:

0.0000519

AC XY:

AN XY:

713420

show subpopulations

Gnomad4 AFR exome

AF:

0.000126

Gnomad4 AMR exome

AF:

0.000298

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000247

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.0000455

Gnomad4 OTH exome

AF:

0.0000507

GnomAD4 genome

AF:

0.0000923

AC:

AN:

151608

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74088

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000591

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.000158

Hom.:

Bravo

AF:

0.000166

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.56

DEOGEN2

Benign

0.019

.;T;.;T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.66

T;T;T;.;T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.024

T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.26

.;.;.;N;N;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.48

N;N;N;N;N;N

REVEL

Benign

0.071

Sift

Benign

0.54

T;T;T;T;T;T

Sift4G

Benign

0.32

T;T;T;T;T;T

Polyphen

0.0010

.;.;B;B;B;.

Vest4

0.091, 0.088, 0.12

MVP

0.13

MPC

0.064

ClinPred

0.0030

GERP RS

-3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.022

gMVP

0.031

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