Genetic Variant CCDC62:p.Arg11Cys (chr12-122774701-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_201435.5(CCDC62):c.31C>T(p.Arg11Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCDC62
NM_201435.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.366

Publications

0 publications found

Variant links:

Genes affected

CCDC62 (HGNC:30723): (coiled-coil domain containing 62) Enables estrogen receptor binding activity and nuclear receptor coactivator activity. Involved in cellular response to estradiol stimulus and positive regulation of transcription by RNA polymerase II. Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CCDC62 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23178777).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201435.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC62	NM_201435.5	MANE Select	c.31C>T	p.Arg11Cys	missense	Exon 1 of 13	NP_958843.2	Q6P9F0-1
	CCDC62	NR_027918.3		n.130C>T		non_coding_transcript_exon	Exon 1 of 13

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC62	ENST00000253079.11	TSL:1 MANE Select	c.31C>T	p.Arg11Cys	missense	Exon 1 of 13	ENSP00000253079.6	Q6P9F0-1
CCDC62	ENST00000392441.8	TSL:5	c.31C>T	p.Arg11Cys	missense	Exon 1 of 12	ENSP00000376236.4	Q6P9F0-2
CCDC62	ENST00000539171.1	TSL:3	c.31C>T	p.Arg11Cys	missense	Exon 1 of 3	ENSP00000439893.1	F5H0F1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1104572

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

523290

African (AFR)

AF:

0.00

AC:

AN:

23448

American (AMR)

AF:

0.00

AC:

AN:

8874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14786

East Asian (EAS)

AF:

0.00

AC:

AN:

27244

South Asian (SAS)

AF:

0.00

AC:

AN:

21764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36014

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4560

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

923718

Other (OTH)

AF:

0.00

AC:

AN:

44164

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152004

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10542

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67970

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

0.0013

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.050

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.79

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.55

PhyloP100

0.37

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-2.1

REVEL

Benign

0.045

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0070

Polyphen

0.098

Vest4

0.16

MutPred

0.33

Gain of loop (P = 0.0013)

MVP

0.41

MPC

1.0

ClinPred

0.68

GERP RS

2.5

PromoterAI

0.11

Neutral

(source)

Varity_R

0.20

gMVP

0.56

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over