chr1-223394461-G-T

Variant names:

• chr1-223394461-G-T
• rs10907376
• NM_152610.3:c.986G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152610.3(CCDC185):​c.986G>T​(p.Gly329Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC185 NM_152610.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.649
• Publications: 20 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040809005).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC185	NM_152610.3	MANE Select	c.986G>T	p.Gly329Val	missense	Exon 1 of 1	NP_689823.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC185	ENST00000366875.5	TSL:6 MANE Select	c.986G>T	p.Gly329Val	missense	Exon 1 of 1	ENSP00000355840.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.04e-7 AC: 1 AN: 1420090 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 702630

African (AFR) AF: 0.00 AC: 0 AN: 32564

American (AMR) AF: 0.00 AC: 0 AN: 37800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25468

East Asian (EAS) AF: 0.00 AC: 0 AN: 37460

South Asian (SAS) AF: 0.00 AC: 0 AN: 81428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.16e-7 AC: 1 AN: 1091580

Other (OTH) AF: 0.00 AC: 0 AN: 58876

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 16138

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.33
DANN	Benign	0.66
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.26	N
PhyloP100		0.65
PROVEAN	Benign	0.41	N
REVEL	Benign	0.022
Sift	Benign	0.36	T
Sift4G	Benign	0.41	T
Polyphen		0.046	B
Vest4		0.052
MutPred		0.19		Loss of catalytic residue at P325 (P = 0.0914)
MVP		0.099
MPC		0.17
ClinPred		0.080	T
GERP RS		-0.73
Varity_R		0.051
gMVP		0.020
Mutation Taster		=100/0	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: rs10907376; hg19: chr1-223567803;