Variant 12-28452493-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018318.5(CCDC91):c.940G>A(p.Val314Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 1,558,316 control chromosomes in the GnomAD database, including 434,438 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.75 ( 42977 hom., cov: 31)

Exomes 𝑓: 0.74 ( 391461 hom. )

Consequence

CCDC91
NM_018318.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.259

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:

CCDC91 (HGNC:):

CCDC91 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.0418315E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC91	NM_018318.5 linkuse as main transcript	c.940G>A	p.Val314Met	missense_variant	11/13	ENST00000536442.6	NP_060788.3	Q7Z6B0-1A0A024RAW6Q05D28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC91	ENST00000536442.6 linkuse as main transcript	c.940G>A	p.Val314Met	missense_variant	11/13	5	NM_018318.5	ENSP00000445660.2		Q7Z6B0-1A0A0A0MTP0

Frequencies

GnomAD3 genomes

AF:

0.749

AC:

113262

AN:

151198

Hom.:

42928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.822

Gnomad AMI

AF:

0.779

Gnomad AMR

AF:

0.664

Gnomad ASJ

AF:

0.685

Gnomad EAS

AF:

0.470

Gnomad SAS

AF:

0.624

Gnomad FIN

AF:

0.737

Gnomad MID

AF:

0.801

Gnomad NFE

AF:

0.759

Gnomad OTH

AF:

0.738

GnomAD3 exomes

AF:

0.705

AC:

156808

AN:

222324

Hom.:

56430

AF XY:

0.706

AC XY:

85571

AN XY:

121148

show subpopulations

Gnomad AFR exome

AF:

0.829

Gnomad AMR exome

AF:

0.609

Gnomad ASJ exome

AF:

0.685

Gnomad EAS exome

AF:

0.467

Gnomad SAS exome

AF:

0.616

Gnomad FIN exome

AF:

0.745

Gnomad NFE exome

AF:

0.763

Gnomad OTH exome

AF:

0.713

GnomAD4 exome

AF:

0.742

AC:

1043947

AN:

1407000

Hom.:

391461

Cov.:

AF XY:

0.738

AC XY:

517220

AN XY:

700510

show subpopulations

Gnomad4 AFR exome

AF:

0.828

Gnomad4 AMR exome

AF:

0.614

Gnomad4 ASJ exome

AF:

0.685

Gnomad4 EAS exome

AF:

0.440

Gnomad4 SAS exome

AF:

0.614

Gnomad4 FIN exome

AF:

0.743

Gnomad4 NFE exome

AF:

0.765

Gnomad4 OTH exome

AF:

0.740

GnomAD4 genome

AF:

0.749

AC:

113365

AN:

151316

Hom.:

42977

Cov.:

AF XY:

0.743

AC XY:

54956

AN XY:

73950

show subpopulations

Gnomad4 AFR

AF:

0.822

Gnomad4 AMR

AF:

0.664

Gnomad4 ASJ

AF:

0.685

Gnomad4 EAS

AF:

0.470

Gnomad4 SAS

AF:

0.624

Gnomad4 FIN

AF:

0.737

Gnomad4 NFE

AF:

0.759

Gnomad4 OTH

AF:

0.737

Alfa

AF:

0.746

Hom.:

100358

Bravo

AF:

0.751

TwinsUK

AF:

0.786

AC:

2915

ALSPAC

AF:

0.776

AC:

2990

ESP6500AA

AF:

0.825

AC:

3626

ESP6500EA

AF:

0.763

AC:

6544

ExAC

AF:

0.710

AC:

86156

Asia WGS

AF:

0.598

AC:

2066

AN:

3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.47

DANN

Benign

0.48

DEOGEN2

Benign

0.0096

.;T;.;T;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.24

T;T;T;.;T;T

MetaRNN

Benign

7.0e-7

T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.26

.;.;.;N;N;.

PrimateAI

Benign

0.31

PROVEAN

Benign

1.6

N;N;N;N;N;N

REVEL

Benign

0.082

Sift

Benign

1.0

T;T;T;T;T;T

Sift4G

Benign

0.96

T;T;T;T;T;T

Polyphen

0.0010, 0.0

.;.;B;B;B;.

Vest4

0.14, 0.11, 0.056

MPC

0.077

ClinPred

0.0020

GERP RS

-5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.047

gMVP

0.028

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over