NM_152610.3:c.139G>A

Variant names:

• chr1-223393614-G-A
• rs901188712
• NM_152610.3:c.139G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152610.3(CCDC185):​c.139G>A​(p.Gly47Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000729 in 1,371,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: CCDC185 NM_152610.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.86

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.027100563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC185	NM_152610.3	c.139G>A	p.Gly47Arg	missense_variant	Exon 1 of 1	ENST00000366875.5	NP_689823.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC185	ENST00000366875.5	c.139G>A	p.Gly47Arg	missense_variant	Exon 1 of 1	6	NM_152610.3	ENSP00000355840.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.29e-7 AC: 1 AN: 1371956 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 674008

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.34e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.80
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.55	N
PROVEAN	Benign	0.69	N
REVEL	Benign	0.012
Sift	Benign	0.74	T
Sift4G	Benign	0.72	T
Polyphen		0.010	B
Vest4		0.076
MutPred		0.078		Gain of methylation at G47 (P = 0.0338);
MVP		0.072
MPC		0.16
ClinPred		0.040	T
GERP RS		-7.1
Varity_R		0.045
gMVP		0.038

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs901188712; hg19: chr1-223566956; COSMIC: COSV64821294;