GeneBe

chr9-15594053-A-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173550.4(CCDC171):​c.556A>G​(p.Lys186Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00009 in 1,588,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K186R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000093 ( 0 hom. )

Consequence

CCDC171
NM_173550.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.13
Variant links:
Genes affected
CCDC171 (HGNC:29828): (coiled-coil domain containing 171)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04793352).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC171NM_173550.4 linkc.556A>G p.Lys186Glu missense_variant Exon 6 of 26 ENST00000380701.8 NP_775821.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC171ENST00000380701.8 linkc.556A>G p.Lys186Glu missense_variant Exon 6 of 26 1 NM_173550.4 ENSP00000370077.3 Q6TFL3-1

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152130
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.000103
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000635
AC:
15
AN:
236208
AF XY:
0.0000782
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000135
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000100
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000933
AC:
134
AN:
1436250
Hom.:
0
Cov.:
26
AF XY:
0.0000951
AC XY:
68
AN XY:
714832
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32152
American (AMR)
AF:
0.0000995
AC:
4
AN:
40186
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25746
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39074
South Asian (SAS)
AF:
0.00
AC:
0
AN:
81754
European-Finnish (FIN)
AF:
0.0000188
AC:
1
AN:
53290
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5720
European-Non Finnish (NFE)
AF:
0.000115
AC:
126
AN:
1098896
Other (OTH)
AF:
0.0000505
AC:
3
AN:
59432
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.429
Heterozygous variant carriers
0
6
12
19
25
31
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<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
AF:
0.0000592
AC:
9
AN:
152130
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74306
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41448
American (AMR)
AF:
0.0000655
AC:
1
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5194
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10616
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.000103
AC:
7
AN:
67986
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.514
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome 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
Alfa
AF:
0.0000540
Hom.:
0
Bravo
AF:
0.0000642
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000577
AC:
7

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 02, 2022
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.556A>G (p.K186E) alteration is located in exon 6 (coding exon 5) of the CCDC171 gene. This alteration results from a A to G substitution at nucleotide position 556, causing the lysine (K) at amino acid position 186 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.024
T
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.44
FATHMM_MKL
Benign
0.56
D
LIST_S2
Benign
0.43
T
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.048
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N
PhyloP100
2.1
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.61
N
REVEL
Benign
0.026
Sift
Benign
0.030
D
Sift4G
Benign
0.98
T
Polyphen
0.0
B
Vest4
0.38
MVP
0.067
ClinPred
0.049
T
GERP RS
2.9
Varity_R
0.072
gMVP
0.046
Mutation Taster
=91/9
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

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Other links and lift over

dbSNP: rs372596980; hg19: chr9-15594051; API