12-122798161-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_201435.5(CCDC62):c.938A>T(p.Tyr313Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000842 in 1,589,394 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0050 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (9 hom.)
• Consequence: CCDC62 NM_201435.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.634

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005215585).
• BP6: Variant 12-122798161-A-T is Benign according to our data. Variant chr12-122798161-A-T is described in ClinVar as [Benign]. Clinvar id is 784263.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00496 (756/152352) while in subpopulation AFR AF= 0.0171 (711/41582). AF 95% confidence interval is 0.0161. There are 5 homozygotes in gnomad4. There are 370 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC62	NM_201435.5	c.938A>T	p.Tyr313Phe	missense_variant	8/13	ENST00000253079.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC62	ENST00000253079.11	c.938A>T	p.Tyr313Phe	missense_variant	8/13	1	NM_201435.5	P3

Frequencies

GnomAD3 genomes AF: 0.00494 AC: 752 AN: 152234 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

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: 0.0000441

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00134 AC: 335 AN: 250574 Hom.: 7 AF XY: 0.000923 AC XY: 125 AN XY: 135412

Gnomad AFR exome AF: 0.0181

Gnomad AMR exome AF: 0.000960

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000330

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000406 AC: 583 AN: 1437042 Hom.: 9 Cov.: 25 AF XY: 0.000331 AC XY: 237 AN XY: 716474

Gnomad4 AFR exome AF: 0.0144

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000468

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000918

Gnomad4 OTH exome AF: 0.000772

GnomAD4 genome AF: 0.00496 AC: 756 AN: 152352 Hom.: 5 Cov.: 32 AF XY: 0.00497 AC XY: 370 AN XY: 74506

Gnomad4 AFR AF: 0.0171

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.000339 Hom.: 0

Bravo AF: 0.00587

ESP6500AA AF: 0.0159 AC: 70

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00180 AC: 218

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	15
Dann	Benign	0.94
DEOGEN2	Benign	0.057	T;.;.;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.45
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.85	T;.;T;T
MetaRNN	Benign	0.0052	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.4	N;N;N;.
REVEL	Benign	0.021
Sift	Benign	0.12	T;T;T;.
Sift4G	Benign	0.13	T;T;D;D
Polyphen		0.84	P;B;B;.
Vest4		0.27
MVP		0.25
MPC		0.21
ClinPred		0.0044	T
GERP RS		2.0
Varity_R		0.095
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs78361567; hg19: chr12-123282708;