NM_152610.3:c.119C>A

Variant names:

• chr1-223393594-C-A
• NM_152610.3:c.119C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152610.3(CCDC185):​c.119C>A​(p.Ser40Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,377,598 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S40F) has been classified as Uncertain significance.

• 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: -0.729

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09978509).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC185	NM_152610.3	c.119C>A	p.Ser40Tyr	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.119C>A	p.Ser40Tyr	missense_variant	Exon 1 of 1	6	NM_152610.3	ENSP00000355840.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1377598 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 677796

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: 0.0000219

Gnomad4 NFE exome AF: 0.00

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	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.6
DANN	Benign	0.85
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.042
Sift	Uncertain	0.025	D
Sift4G	Benign	0.10	T
Polyphen		0.89	P
Vest4		0.12
MutPred		0.13		Loss of glycosylation at S40 (P = 0.0224);
MVP		0.16
MPC		0.20
ClinPred		0.17	T
GERP RS		0.27
Varity_R		0.061
gMVP		0.046

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-223566936;