Variant 11-32613505-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001008391.4(CCDC73):c.2813A>T(p.Asp938Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

CCDC73
NM_001008391.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.803

Variant links:

Genes affected

CCDC73 (HGNC:23261): (coiled-coil domain containing 73)

CCDC73 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=0.036134332).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC73	NM_001008391.4 linkuse as main transcript	c.2813A>T	p.Asp938Val	missense_variant	16/18	ENST00000335185.10	NP_001008392.2	Q6ZRK6-1
CCDC73	XM_047427029.1 linkuse as main transcript	c.2813A>T	p.Asp938Val	missense_variant	21/23		XP_047282985.1
CCDC73	XM_047427030.1 linkuse as main transcript	c.2813A>T	p.Asp938Val	missense_variant	16/18		XP_047282986.1
CCDC73	XM_047427031.1 linkuse as main transcript	c.2555A>T	p.Asp852Val	missense_variant	15/17		XP_047282987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC73	ENST00000335185.10 linkuse as main transcript	c.2813A>T	p.Asp938Val	missense_variant	16/18	2	NM_001008391.4	ENSP00000335325.5		Q6ZRK6-1
CCDC73	ENST00000528333.1 linkuse as main transcript	c.136-10485A>T		intron_variant		3		ENSP00000434365.1		H0YDV2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

249496

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135364

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000222

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1461824

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000414

AC:

Asia WGS

AF:

0.00318

AC:

AN:

3478

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 28, 2023

The c.2813A>T (p.D938V) alteration is located in exon 16 (coding exon 15) of the CCDC73 gene. This alteration results from a A to T substitution at nucleotide position 2813, causing the aspartic acid (D) at amino acid position 938 to be replaced by a valine (V). 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

0.086

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0065

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.70

M_CAP

Benign

0.0093

MetaRNN

Benign

0.036

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.49

REVEL

Benign

0.017

Sift

Uncertain

0.026

Sift4G

Benign

0.19

Polyphen

0.0030

Vest4

0.19

MutPred

0.22

Loss of ubiquitination at K943 (P = 0.0272);

MVP

0.072

MPC

0.16

ClinPred

0.027

GERP RS

0.95

Varity_R

0.088

gMVP

0.13

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