NM_001080539.2:c.371A>C

Variant names:

• chr2-196656827-A-C
• rs368606812
• NM_001080539.2:c.371A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080539.2(CCDC150):​c.371A>C​(p.Glu124Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. E124K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CCDC150 NM_001080539.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.73
• Publications: 0 publications found

Genes affected

CCDC150 (HGNC:26834): (coiled-coil domain containing 150)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3322449).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC150	NM_001080539.2	c.371A>C	p.Glu124Ala	missense_variant	Exon 3 of 28	ENST00000389175.9	NP_001074008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC150	ENST00000389175.9	c.371A>C	p.Glu124Ala	missense_variant	Exon 3 of 28	5	NM_001080539.2	ENSP00000373827.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461578 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727078

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111788

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.7
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.13
Sift	Benign	0.082	T
Sift4G	Uncertain	0.017	D
Polyphen		0.37	B
Vest4		0.65
MutPred		0.17		Loss of ubiquitination at K125 (P = 0.0454);
MVP		0.072
MPC		0.20
ClinPred		0.97	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.27
Mutation Taster		=65/35	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: rs368606812; hg19: chr2-197521551;