chr2-96761008-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_020184.4(CNNM4):​c.9G>T​(p.Pro3Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000887 in 1,014,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

CNNM4
NM_020184.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.42
Variant links:
Genes affected
CNNM4 (HGNC:105): (cyclin and CBS domain divalent metal cation transport mediator 4) This gene encodes a member of the ancient conserved domain containing protein family. Members of this protein family contain a cyclin box motif and have structural similarity to the cyclins. The encoded protein may play a role in metal ion transport. Mutations in this gene are associated with Jalili syndrome which consists of cone-rod dystrophy and amelogenesis imperfecta. [provided by RefSeq, Feb 2010]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 2-96761008-G-T is Benign according to our data. Variant chr2-96761008-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1536521.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=2.42 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CNNM4NM_020184.4 linkc.9G>T p.Pro3Pro synonymous_variant Exon 1 of 7 ENST00000377075.3 NP_064569.3 Q6P4Q7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CNNM4ENST00000377075.3 linkc.9G>T p.Pro3Pro synonymous_variant Exon 1 of 7 1 NM_020184.4 ENSP00000366275.2 Q6P4Q7-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000887
AC:
9
AN:
1014850
Hom.:
0
Cov.:
30
AF XY:
0.0000105
AC XY:
5
AN XY:
477852
show subpopulations
Gnomad4 AFR exome
AF:
0.00
AC:
0
AN:
20490
Gnomad4 AMR exome
AF:
0.00
AC:
0
AN:
6186
Gnomad4 ASJ exome
AF:
0.00
AC:
0
AN:
11354
Gnomad4 EAS exome
AF:
0.00
AC:
0
AN:
20012
Gnomad4 SAS exome
AF:
0.000158
AC:
3
AN:
18932
Gnomad4 FIN exome
AF:
0.00
AC:
0
AN:
19214
Gnomad4 NFE exome
AF:
0.00000456
AC:
4
AN:
877308
Gnomad4 Remaining exome
AF:
0.0000516
AC:
2
AN:
38784
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Aug 04, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
13
DANN
Benign
0.78
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.0
Mutation Taster
=100/0
polymorphism

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: rs1381328427; hg19: chr2-97426745; API