17-16708868-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001382000.1(CCDC144A):​c.811C>T​(p.His271Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,611,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

CCDC144A
NM_001382000.1 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.540
Variant links:
Genes affected
CCDC144A (HGNC:29072): (coiled-coil domain containing 144A)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.040569484).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC144ANM_001382000.1 linkc.811C>T p.His271Tyr missense_variant Exon 5 of 17 ENST00000399273.5 NP_001368929.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC144AENST00000399273.5 linkc.811C>T p.His271Tyr missense_variant Exon 5 of 17 1 NM_001382000.1 ENSP00000382215.1 C9JT67
ENSG00000266302ENST00000448331.7 linkn.811C>T non_coding_transcript_exon_variant Exon 5 of 26 2 ENSP00000440655.2 C9JT67

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152098
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000283
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000723
AC:
18
AN:
248858
Hom.:
0
AF XY:
0.0000888
AC XY:
12
AN XY:
135130
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000464
Gnomad NFE exome
AF:
0.0000532
Gnomad OTH exome
AF:
0.000331
GnomAD4 exome
AF:
0.0000295
AC:
43
AN:
1459568
Hom.:
0
Cov.:
32
AF XY:
0.0000317
AC XY:
23
AN XY:
726080
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000599
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000831
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152216
Hom.:
0
Cov.:
31
AF XY:
0.0000134
AC XY:
1
AN XY:
74416
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000283
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000117
Hom.:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000122
AC:
1
ExAC
AF:
0.000124
AC:
15

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 27, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.811C>T (p.H271Y) alteration is located in exon 5 (coding exon 5) of the CCDC144A gene. This alteration results from a C to T substitution at nucleotide position 811, causing the histidine (H) at amino acid position 271 to be replaced by a tyrosine (Y). 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
0.084
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
0.15
DANN
Benign
0.96
DEOGEN2
Benign
0.0012
.;.;.;T
Eigen
Benign
-0.96
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.00034
N
LIST_S2
Benign
0.53
T;T;T;T
M_CAP
Benign
0.0025
T
MetaRNN
Benign
0.041
T;T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-0.91
N;N;.;N
REVEL
Benign
0.039
Sift
Benign
0.053
T;D;.;D
Sift4G
Uncertain
0.051
T;T;D;T
Polyphen
0.80
.;.;.;P
Vest4
0.10
MVP
0.014
ClinPred
0.035
T
GERP RS
0.27
Varity_R
0.044
gMVP
0.015

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: rs200353361; hg19: chr17-16612182; COSMIC: COSV60696427; COSMIC: COSV60696427; API