2-196656787-A-T

Variant names:

• chr2-196656787-A-T
• NM_001080539.2:c.331A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080539.2(CCDC150):​c.331A>T​(p.Met111Leu) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M111T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC150 NM_001080539.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.93
• Publications: 0 publications found

Genes affected

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

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=0.06268704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC150	NM_001080539.2	c.331A>T	p.Met111Leu	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.331A>T	p.Met111Leu	missense_variant	Exon 3 of 28	5	NM_001080539.2	ENSP00000373827.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.331A>T (p.M111L) alteration is located in exon 3 (coding exon 3) of the CCDC150 gene. This alteration results from a A to T substitution at nucleotide position 331, causing the methionine (M) at amino acid position 111 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Benign	0.56
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.9
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.017
Sift	Uncertain	0.024	D
Sift4G	Benign	0.13	T
Polyphen		0.0	B
Vest4		0.25
MutPred		0.27		Loss of catalytic residue at M111 (P = 0.0228);
MVP		0.014
MPC		0.032
ClinPred		0.067	T
GERP RS		2.7
Varity_R		0.098
gMVP		0.072
Mutation Taster		=93/7	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

hg19: chr2-197521511;