Variant 12-122774686-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_201435.5(CCDC62):c.16G>A(p.Ala6Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000906 in 1,104,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 9.1e-7 ( 0 hom. )

Consequence

CCDC62
NM_201435.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0730

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03482741).

BP6

Variant 12-122774686-G-A is Benign according to our data. Variant chr12-122774686-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3139245.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC62	NM_201435.5 linkuse as main transcript	c.16G>A	p.Ala6Thr	missense_variant	1/13	ENST00000253079.11	NP_958843.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC62	ENST00000253079.11 linkuse as main transcript	c.16G>A	p.Ala6Thr	missense_variant	1/13	1	NM_201435.5	ENSP00000253079	P3	Q6P9F0-1
CCDC62	ENST00000392441.8 linkuse as main transcript	c.16G>A	p.Ala6Thr	missense_variant	1/12	5		ENSP00000376236	A2	Q6P9F0-2
CCDC62	ENST00000539171.1 linkuse as main transcript	c.16G>A	p.Ala6Thr	missense_variant	1/3	3		ENSP00000439893
CCDC62	ENST00000341952.8 linkuse as main transcript	c.16G>A	p.Ala6Thr	missense_variant, NMD_transcript_variant	1/13	2		ENSP00000341471		Q6P9F0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.06e-7

AC:

AN:

1104302

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

523136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.8

DANN

Benign

0.96

DEOGEN2

Benign

0.011

T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.51

T;.;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.035

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.51

N;N;N

REVEL

Benign

0.017

Sift

Benign

1.0

T;T;D

Sift4G

Benign

1.0

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.024

MutPred

0.20

Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);

MVP

0.088

MPC

0.22

ClinPred

0.11

GERP RS

-3.4

Varity_R

0.048

gMVP

0.39

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over