12-122774701-C-T

Variant names:

• chr12-122774701-C-T
• rs538615250
• NM_201435.5:c.31C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.366
• Publications: 0 publications found

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

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

Sel.	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: 1 AN: 152004 Hom.: 0 Cov.: 31

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: 0 AN: 1104572 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 523290

African (AFR) AF: 0.00 AC: 0 AN: 23448

American (AMR) AF: 0.00 AC: 0 AN: 8874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14786

East Asian (EAS) AF: 0.00 AC: 0 AN: 27244

South Asian (SAS) AF: 0.00 AC: 0 AN: 21764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4560

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 923718

Other (OTH) AF: 0.00 AC: 0 AN: 44164

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152004 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74244

African (AFR) AF: 0.0000241 AC: 1 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67970

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	0.0013	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.37
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.045
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.098	B
Vest4		0.16
MutPred		0.33		Gain of loop (P = 0.0013)
MVP		0.41
MPC		1.0
ClinPred		0.68	D
GERP RS		2.5
PromoterAI		0.11	Neutral
Varity_R		0.20
gMVP		0.56
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs538615250; hg19: chr12-123259248;