NM_001080433.2:c.95C>T

Variant names:

• chr2-56184719-C-T
• rs1675922285
• NM_001080433.2:c.95C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080433.2(CCDC85A):​c.95C>T​(p.Pro32Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000915 in 1,530,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000094 (0 hom.)
• Consequence: CCDC85A NM_001080433.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08
• Publications: 0 publications found

Genes affected

CCDC85A (HGNC:29400): (coiled-coil domain containing 85A) Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000233251 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15690902).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080433.2. 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
	CCDC85A	NM_001080433.2	MANE Select	c.95C>T	p.Pro32Leu	missense	Exon 1 of 6	NP_001073902.1	Q96PX6
	CCDC85A	NM_001348512.1		c.95C>T	p.Pro32Leu	missense	Exon 1 of 7	NP_001335441.1
	CCDC85A	NM_001348513.1		c.95C>T	p.Pro32Leu	missense	Exon 1 of 6	NP_001335442.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC85A	ENST00000407595.3	TSL:1 MANE Select	c.95C>T	p.Pro32Leu	missense	Exon 1 of 6	ENSP00000384040.2	Q96PX6
	ENSG00000233251	ENST00000432793.6	TSL:1	n.100+979G>A		intron	N/A
	CCDC85A	ENST00000894231.1		c.95C>T	p.Pro32Leu	missense	Exon 1 of 7	ENSP00000564290.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152086 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000943 AC: 13 AN: 1378730 Hom.: 0 Cov.: 35 AF XY: 0.00000735 AC XY: 5 AN XY: 680132

African (AFR) AF: 0.00 AC: 0 AN: 28452

American (AMR) AF: 0.00 AC: 0 AN: 34566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24542

East Asian (EAS) AF: 0.00 AC: 0 AN: 33696

South Asian (SAS) AF: 0.00 AC: 0 AN: 77410

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44580

Middle Eastern (MID) AF: 0.000229 AC: 1 AN: 4366

European-Non Finnish (NFE) AF: 0.0000102 AC: 11 AN: 1073874

Other (OTH) AF: 0.0000175 AC: 1 AN: 57244

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152086 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74280

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.34	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.1
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.031
Sift	Uncertain	0.023	D
Sift4G	Benign	0.080	T
Polyphen		0.52	P
Vest4		0.051
MutPred		0.43		Gain of helix (P = 0.0022)
MVP		0.28
MPC		0.087
ClinPred		0.71	D
GERP RS		1.5
Varity_R		0.047
gMVP		0.29
Mutation Taster		=85/15	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: rs1675922285; hg19: chr2-56411854;