14-59531887-T-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001164399.2(CCDC175):​c.1647A>T​(p.Gln549His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,236,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000065 ( 0 hom. )

Consequence

CCDC175
NM_001164399.2 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.95

Publications

0 publications found
Variant links:
Genes affected
CCDC175 (HGNC:19847): (coiled-coil domain containing 175)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.061613053).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC175NM_001164399.2 linkc.1647A>T p.Gln549His missense_variant Exon 14 of 20 ENST00000537690.7 NP_001157871.1 P0C221

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC175ENST00000537690.7 linkc.1647A>T p.Gln549His missense_variant Exon 14 of 20 5 NM_001164399.2 ENSP00000453940.1 P0C221
CCDC175ENST00000281581.5 linkc.1647A>T p.Gln549His missense_variant Exon 14 of 20 5 ENSP00000452964.1 A0A0A0MTQ8

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152234
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000523
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:
0.00
Gnomad OTH
AF:
0.000478
GnomAD2 exomes
AF:
0.0000162
AC:
2
AN:
123826
AF XY:
0.0000152
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000541
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000186
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000646
AC:
7
AN:
1084252
Hom.:
0
Cov.:
17
AF XY:
0.00000732
AC XY:
4
AN XY:
546218
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
24712
American (AMR)
AF:
0.000173
AC:
5
AN:
28922
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22656
East Asian (EAS)
AF:
0.00
AC:
0
AN:
34190
South Asian (SAS)
AF:
0.00
AC:
0
AN:
68000
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
34674
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4808
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
818752
Other (OTH)
AF:
0.0000421
AC:
2
AN:
47538
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.561
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152352
Hom.:
0
Cov.:
32
AF XY:
0.0000671
AC XY:
5
AN XY:
74494
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41594
American (AMR)
AF:
0.000523
AC:
8
AN:
15306
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5190
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4818
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68034
Other (OTH)
AF:
0.000473
AC:
1
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.581
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.000170

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 14, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.1647A>T (p.Q549H) alteration is located in exon 14 (coding exon 14) of the CCDC175 gene. This alteration results from a A to T substitution at nucleotide position 1647, causing the glutamine (Q) at amino acid position 549 to be replaced by a histidine (H). 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
0.20
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.012
T;T
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.42
N
LIST_S2
Benign
0.66
T;T
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.062
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
L;.
PhyloP100
1.9
PrimateAI
Benign
0.40
T
PROVEAN
Uncertain
-2.5
D;N
Sift
Uncertain
0.021
D;D
Sift4G
Uncertain
0.051
T;T
Vest4
0.16
MVP
0.030
ClinPred
0.59
D
GERP RS
3.8
Varity_R
0.11
gMVP
0.059
Mutation Taster
=95/5
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs533148415; hg19: chr14-59998605; API