chr12-28452517-G-A

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

19

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]

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
CCDC91NM_018318.5 linkuse as main transcriptc.964G>A p.Val322Ile missense_variant 11/13 ENST00000536442.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCDC91ENST00000536442.6 linkuse as main transcriptc.964G>A p.Val322Ile missense_variant 11/135 NM_018318.5 P1Q7Z6B0-1

Frequencies

GnomAD3 genomes
AF:
0.0000924
AC:
14
AN:
151490
Hom.:
0
Cov.:
32
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:
24
AN:
234850
Hom.:
0
AF XY:
0.000110
AC XY:
14
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:
72
AN:
1433774
Hom.:
0
Cov.:
29
AF XY:
0.0000519
AC XY:
37
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:
14
AN:
151608
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
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.:
0
Bravo
AF:
0.000166
ExAC
AF:
0.0000741
AC:
9

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 submitterclinical testingAmbry GeneticsDec 28, 2022This 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
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
14
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
N
LIST_S2
Benign
0.66
T;T;T;.;T;T
M_CAP
Benign
0.0043
T
MetaRNN
Benign
0.024
T;T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.26
.;.;.;N;N;.
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.27
T
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
T
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.

Other links and lift over

dbSNP: rs760444503; hg19: chr12-28605450; COSMIC: COSV60339920; COSMIC: COSV60339920; API