rs368408614

Variant names:

• chr1-223393663-A-C
• rs368408614
• NM_152610.3:c.188A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152610.3(CCDC185):​c.188A>C​(p.His63Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000454 in 1,565,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H63R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000033 (0 hom.)
• Consequence: CCDC185 NM_152610.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.202
• Publications: 0 publications found

Genes affected

CCDC185 (HGNC:26654): (coiled-coil domain containing 185)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013402909).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152610.3. 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
	CCDC185	NM_152610.3	MANE Select	c.188A>C	p.His63Pro	missense	Exon 1 of 1	NP_689823.2	Q8N715

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC185	ENST00000366875.5	TSL:6 MANE Select	c.188A>C	p.His63Pro	missense	Exon 1 of 1	ENSP00000355840.3	Q8N715

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000579

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

GnomAD2 exomes AF: 0.0000265 AC: 5 AN: 188538 AF XY: 0.00000958

Gnomad AFR exome AF: 0.000402

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000333 AC: 47 AN: 1412792 Hom.: 0 Cov.: 31 AF XY: 0.0000329 AC XY: 23 AN XY: 698870

African (AFR) AF: 0.000930 AC: 30 AN: 32256

American (AMR) AF: 0.00 AC: 0 AN: 38952

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23158

East Asian (EAS) AF: 0.00 AC: 0 AN: 39198

South Asian (SAS) AF: 0.00 AC: 0 AN: 78534

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4718

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1092564

Other (OTH) AF: 0.000275 AC: 16 AN: 58188

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74450

African (AFR) AF: 0.000577 AC: 24 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000147

ExAC AF: 0.0000427 AC: 5

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	0.065
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.0
DANN	Benign	0.51
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.20
PROVEAN	Benign	0.29	N
REVEL	Benign	0.013
Sift	Benign	0.16	T
Sift4G	Benign	0.30	T
Polyphen		0.0020	B
Vest4		0.18
MutPred		0.14		Loss of MoRF binding (P = 0.0761)
MVP		0.067
MPC		0.21
ClinPred		0.019	T
GERP RS		-5.9
PromoterAI		0.19	Neutral
Varity_R		0.043
gMVP		0.048
Mutation Taster		=98/2	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: rs368408614; hg19: chr1-223567005;