7-23643042-C-G

Variant names:

• chr7-23643042-C-G
• NM_138771.4:c.350C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138771.4(CCDC126):​c.350C>G​(p.Thr117Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 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: CCDC126 NM_138771.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.20

Genes affected

CCDC126 (HGNC:22398): (coiled-coil domain containing 126) Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13730353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC126	NM_138771.4	c.350C>G	p.Thr117Ser	missense_variant	Exon 4 of 4	ENST00000307471.8	NP_620126.2
CCDC126	XM_017012775.3	c.350C>G	p.Thr117Ser	missense_variant	Exon 5 of 5		XP_016868264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC126	ENST00000307471.8	c.350C>G	p.Thr117Ser	missense_variant	Exon 4 of 4	1	NM_138771.4	ENSP00000304355.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.350C>G (p.T117S) alteration is located in exon 4 (coding exon 2) of the CCDC126 gene. This alteration results from a C to G substitution at nucleotide position 350, causing the threonine (T) at amino acid position 117 to be replaced by a serine (S). 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	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.010	T;T;T
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.67	.;.;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.7	L;L;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.15	N;N;N
REVEL	Benign	0.077
Sift	Benign	0.30	T;T;T
Sift4G	Benign	0.55	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.20
MutPred		0.17		Gain of disorder (P = 0.0831);Gain of disorder (P = 0.0831);Gain of disorder (P = 0.0831);
MVP		0.13
MPC		0.18
ClinPred		0.79	D
GERP RS		5.9
Varity_R		0.050
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-23682661;