Genetic Variant CCDC144A:p.His271Tyr (chr17-16708868-C-T) – ACMG Classification: Likely_benign (-2 pts)

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

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)

CCDC144A links:

ENSG00000266302 (HGNC:):

ENSG00000266302 links:

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
CCDC144A	NM_001382000.1 link	c.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
CCDC144A	ENST00000399273.5 link	c.811C>T	p.His271Tyr	missense_variant	Exon 5 of 17	1	NM_001382000.1	ENSP00000382215.1		C9JT67
ENSG00000266302	ENST00000448331.7 link	n.811C>T		non_coding_transcript_exon_variant	Exon 5 of 26	2		ENSP00000440655.2		C9JT67

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152098

Hom.:

Cov.:

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:

AN:

248858

Hom.:

AF XY:

0.0000888

AC XY:

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:

AN:

1459568

Hom.:

Cov.:

AF XY:

0.0000317

AC XY:

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:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

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.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.000124

AC:

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

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

LIST_S2

Benign

0.53

T;T;T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.041

T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.61

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over