2-196674283-T-G

Variant summary

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

The NM_001080539.2(CCDC150):c.1072T>G(p.Cys358Gly) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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: 0.230

Genes affected

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

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=0.038113892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC150	NM_001080539.2	c.1072T>G	p.Cys358Gly	missense_variant	10/28	ENST00000389175.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC150	ENST00000389175.9	c.1072T>G	p.Cys358Gly	missense_variant	10/28	5	NM_001080539.2	A2
CCDC150	ENST00000495513.1	n.537T>G		non_coding_transcript_exon_variant	6/7	3
CCDC150	ENST00000498512.5	n.364T>G		non_coding_transcript_exon_variant	4/5	5
CCDC150	ENST00000431807.6	c.*218T>G		3_prime_UTR_variant, NMD_transcript_variant	6/23	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2022

The c.1072T>G (p.C358G) alteration is located in exon 10 (coding exon 10) of the CCDC150 gene. This alteration results from a T to G substitution at nucleotide position 1072, causing the cysteine (C) at amino acid position 358 to be replaced by a glycine (G). 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	0.059
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	15
Dann	Benign	0.84
DEOGEN2	Benign	0.00071	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.51	N
REVEL	Benign	0.010
Sift	Benign	0.10	T
Sift4G	Benign	0.13	T
Polyphen		0.0040	B
Vest4		0.17
MutPred		0.19		Gain of disorder (P = 0.0945);
MVP		0.048
MPC		0.040
ClinPred		0.028	T
GERP RS		1.4
Varity_R		0.068
gMVP		0.019

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: rs1694367651; hg19: chr2-197539007;