12-122777496-C-T

Variant names:

• chr12-122777496-C-T
• rs61956960
• NM_201435.5:c.42C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_201435.5(CCDC62):​c.42C>T​(p.Ile14Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,606,116 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0084 (5 hom., cov: 32)
  • Exomes 𝑓: 0.012 (148 hom.)
• Consequence: CCDC62 NM_201435.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.391
• Publications: 4 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 12-122777496-C-T is Benign according to our data. Variant chr12-122777496-C-T is described in ClinVar as Benign. ClinVar VariationId is 2643506.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.391 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.42C>T	p.Ile14Ile	synonymous	Exon 2 of 13	NP_958843.2	Q6P9F0-1
	CCDC62	NR_027918.3		n.141C>T		non_coding_transcript_exon	Exon 2 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC62	ENST00000253079.11	TSL:1 MANE Select	c.42C>T	p.Ile14Ile	synonymous	Exon 2 of 13	ENSP00000253079.6	Q6P9F0-1
	CCDC62	ENST00000537566.5	TSL:2	c.-264C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000445045.1	Q6P9F0-3
	CCDC62	ENST00000392441.8	TSL:5	c.42C>T	p.Ile14Ile	synonymous	Exon 2 of 12	ENSP00000376236.4	Q6P9F0-2

Frequencies

GnomAD3 genomes AF: 0.00843 AC: 1282 AN: 152132 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00232

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00767

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00594

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.00955

GnomAD2 exomes AF: 0.00803 AC: 1988 AN: 247460 AF XY: 0.00818

Gnomad AFR exome AF: 0.00216

Gnomad AMR exome AF: 0.00414

Gnomad ASJ exome AF: 0.00827

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00552

Gnomad NFE exome AF: 0.0133

Gnomad OTH exome AF: 0.00978

GnomAD4 exome AF: 0.0123 AC: 17914 AN: 1453866 Hom.: 148 Cov.: 30 AF XY: 0.0119 AC XY: 8592 AN XY: 722166

African (AFR) AF: 0.00187 AC: 62 AN: 33196

American (AMR) AF: 0.00481 AC: 210 AN: 43658

Ashkenazi Jewish (ASJ) AF: 0.00782 AC: 203 AN: 25974

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39546

South Asian (SAS) AF: 0.00209 AC: 178 AN: 85144

European-Finnish (FIN) AF: 0.00593 AC: 316 AN: 53318

Middle Eastern (MID) AF: 0.00888 AC: 51 AN: 5744

European-Non Finnish (NFE) AF: 0.0147 AC: 16281 AN: 1107232

Other (OTH) AF: 0.0102 AC: 611 AN: 60054

GnomAD4 genome AF: 0.00843 AC: 1283 AN: 152250 Hom.: 5 Cov.: 32 AF XY: 0.00763 AC XY: 568 AN XY: 74444

African (AFR) AF: 0.00231 AC: 96 AN: 41550

American (AMR) AF: 0.00766 AC: 117 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4824

European-Finnish (FIN) AF: 0.00594 AC: 63 AN: 10600

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0139 AC: 946 AN: 68020

Other (OTH) AF: 0.00945 AC: 20 AN: 2116

Alfa AF: 0.0112 Hom.: 4

Bravo AF: 0.00901

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0139

EpiControl AF: 0.0138

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	6.7
DANN	Benign	0.84
PhyloP100		0.39
Mutation Taster		=300/0	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: rs61956960; hg19: chr12-123262043; COSMIC: COSV53432879;