12-48184542-A-T

Position:

• chr12-48184542-A-T

Variant summary

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

The NM_001013635.4(CCDC184):​c.420A>T​(p.Glu140Asp) 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. 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000029 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC184 NM_001013635.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

Genes affected

CCDC184 (HGNC:33749): (coiled-coil domain containing 184) Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.015705884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC184	NM_001013635.4	c.420A>T	p.Glu140Asp	missense_variant	1/1	ENST00000316554.5	NP_001013657.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC184	ENST00000316554.5	c.420A>T	p.Glu140Asp	missense_variant	1/1	6	NM_001013635.4	ENSP00000320849.3

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000285 AC: 4 AN: 1402180 Hom.: 0 Cov.: 74 AF XY: 0.00000433 AC XY: 3 AN XY: 693166

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: 0.00000368

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.0
DANN	Benign	0.60
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PROVEAN	Benign	0.80	N
REVEL	Benign	0.024
Sift	Benign	1.0	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.033
MutPred		0.084		Loss of helix (P = 0.0444);
MVP		0.043
MPC		0.34
ClinPred		0.037	T
GERP RS		-1.7
Varity_R		0.049
gMVP		0.024

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

LitVar

Other links and lift over

dbSNP: rs10783231; hg19: chr12-48578325;