Variant 6-37483214-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_138493.3(CCDC167):c.266C>T(p.Thr89Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,614,042 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000040 ( 1 hom. )

Consequence

CCDC167
NM_138493.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.539

Variant links:

Genes affected

CCDC167 (HGNC:21239): (coiled-coil domain containing 167) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CCDC167 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=0.07930589).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC167	NM_138493.3 linkuse as main transcript	c.266C>T	p.Thr89Met	missense_variant	4/4	ENST00000373408.4	NP_612502.1	Q9P0B6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC167	ENST00000373408.4 linkuse as main transcript	c.266C>T	p.Thr89Met	missense_variant	4/4	1	NM_138493.3	ENSP00000362507.3		Q9P0B6

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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:

0.0000517

AC:

AN:

251478

Hom.:

AF XY:

0.0000809

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000397

AC:

AN:

1461704

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0000962

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:

0.0000282

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Nov 23, 2024

The c.266C>T (p.T89M) alteration is located in exon 4 (coding exon 4) of the CCDC167 gene. This alteration results from a C to T substitution at nucleotide position 266, causing the threonine (T) at amino acid position 89 to be replaced by a methionine (M). 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

0.10

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.042

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.79

M_CAP

Benign

0.013

MetaRNN

Benign

0.079

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.14

REVEL

Benign

0.041

Sift

Benign

0.22

Sift4G

Benign

0.086

Polyphen

0.57

Vest4

0.21

MutPred

0.27

Loss of catalytic residue at T89 (P = 0.1769);

MVP

0.014

MPC

0.34

ClinPred

0.047

GERP RS

0.91

Varity_R

0.017

gMVP

0.42

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