Variant 11-27350364-G-T 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_030771.2(CCDC34):c.574C>A(p.His192Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000625 in 1,613,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00062 ( 0 hom. )

Consequence

CCDC34
NM_030771.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.60

Variant links:

Genes affected

CCDC34 (HGNC:25079): (coiled-coil domain containing 34)

CCDC34 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=0.17707881).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC34	NM_030771.2 linkuse as main transcript	c.574C>A	p.His192Asn	missense_variant	3/6	ENST00000328697.11	NP_110398.1
CCDC34	NM_080654.3 linkuse as main transcript	c.574C>A	p.His192Asn	missense_variant	3/3		NP_542385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC34	ENST00000328697.11 linkuse as main transcript	c.574C>A	p.His192Asn	missense_variant	3/6	1	NM_030771.2	ENSP00000330240	P1	Q96HJ3-1
CCDC34	ENST00000317945.6 linkuse as main transcript	c.574C>A	p.His192Asn	missense_variant	3/3	1		ENSP00000321563		Q96HJ3-2
CCDC34	ENST00000529615.1 linkuse as main transcript	n.61C>A		non_coding_transcript_exon_variant	1/6	3

Frequencies

GnomAD3 genomes

AF:

0.000645

AC:

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000568

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000466

AC:

117

AN:

251002

Hom.:

AF XY:

0.000435

AC XY:

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.000767

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.000623

AC:

911

AN:

1461424

Hom.:

Cov.:

AF XY:

0.000607

AC XY:

441

AN XY:

726990

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000468

Gnomad4 NFE exome

AF:

0.000762

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.000645

AC:

AN:

152006

Hom.:

Cov.:

AF XY:

0.000620

AC XY:

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000568

Gnomad4 NFE

AF:

0.00121

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000807

Hom.:

Bravo

AF:

0.000525

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000338

AC:

EpiCase

AF:

0.00109

EpiControl

AF:

0.000771

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

Feb 14, 2024

The c.574C>A (p.H192N) alteration is located in exon 3 (coding exon 3) of the CCDC34 gene. This alteration results from a C to A substitution at nucleotide position 574, causing the histidine (H) at amino acid position 192 to be replaced by an asparagine (N). 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

Pathogenic

0.75

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.066

T;.

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.0098

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.6

M;M

MutationTaster

Benign

0.81

D;D

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.19

Sift

Benign

0.20

T;T

Sift4G

Benign

0.43

T;T

Polyphen

0.99

D;D

Vest4

0.55

MVP

0.73

MPC

0.61

ClinPred

0.090

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.26

gMVP

0.22

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