Variant 13-36295796-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001144981.3(CCDC169):c.145C>T(p.Leu49Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,533,178 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000043 ( 1 hom. )

Consequence

CCDC169
NM_001144981.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08

Variant links:

Genes affected

CCDC169 (HGNC:34361): (coiled-coil domain containing 169)

CCDC169 links:

CCDC169-SOHLH2 (HGNC:):

CCDC169-SOHLH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09536648).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC169	NM_001144981.3 linkuse as main transcript	c.145C>T	p.Leu49Phe	missense_variant	2/8	ENST00000239859.8	NP_001138453.1
CCDC169-SOHLH2	NM_001198910.2 linkuse as main transcript	c.-97+1841C>T		intron_variant			NP_001185839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC169	ENST00000239859.8 linkuse as main transcript	c.145C>T	p.Leu49Phe	missense_variant	2/8	5	NM_001144981.3	ENSP00000239859	P1	A6NNP5-1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000128

AC:

AN:

155684

Hom.:

AF XY:

0.0000122

AC XY:

AN XY:

82288

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000418

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000434

AC:

AN:

1381028

Hom.:

Cov.:

AF XY:

0.00000293

AC XY:

AN XY:

682204

show subpopulations

Gnomad4 AFR exome

AF:

0.000160

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:

0.00

Gnomad4 NFE exome

AF:

9.40e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.000290

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 05, 2024

The c.145C>T (p.L49F) alteration is located in exon 2 (coding exon 2) of the CCDC169 gene. This alteration results from a C to T substitution at nucleotide position 145, causing the leucine (L) at amino acid position 49 to be replaced by a phenylalanine (F). 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

0.19

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

.;T

Eigen

Benign

0.031

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.095

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.2

L;L

MutationTaster

Benign

0.80

D;D;D;D;D;D;D;D;D

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.042

Sift

Benign

0.27

T;T

Sift4G

Uncertain

0.030

D;D

Polyphen

0.76

P;P

Vest4

0.24

MVP

0.22

ClinPred

0.32

GERP RS

3.2

Varity_R

0.058

gMVP

0.096

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