1-223393621-C-T

Variant names:

• chr1-223393621-C-T
• rs748221522
• NM_152610.3:c.146C>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.146C>T​(p.Pro49Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,373,674 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. 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. P49Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: CCDC185 NM_152610.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646
• Publications: 0 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=0.047791094).

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.146C>T	p.Pro49Leu	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.146C>T	p.Pro49Leu	missense	Exon 1 of 1	ENSP00000355840.3	Q8N715

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1373674 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 675094

African (AFR) AF: 0.00 AC: 0 AN: 29700

American (AMR) AF: 0.00 AC: 0 AN: 33774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21094

East Asian (EAS) AF: 0.0000267 AC: 1 AN: 37404

South Asian (SAS) AF: 0.00 AC: 0 AN: 73950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44832

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4620

European-Non Finnish (NFE) AF: 9.33e-7 AC: 1 AN: 1071762

Other (OTH) AF: 0.00 AC: 0 AN: 56538

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.6
DANN	Benign	0.93
DEOGEN2	Benign	0.049	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		-0.65
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.0070
Sift	Benign	0.11	T
Sift4G	Benign	0.49	T
Polyphen		0.0010	B
Vest4		0.068
MutPred		0.18		Gain of stability (P = 0.0553)
MVP		0.10
MPC		0.13
ClinPred		0.032	T
GERP RS		0.54
PromoterAI		0.021	Neutral
Varity_R		0.035
gMVP		0.052
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs748221522; hg19: chr1-223566963;