7-23611532-G-T

Position:

• chr7-23611532-G-T

Variant summary

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

The NM_138771.4(CCDC126):​c.217G>T​(p.Gly73Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 9.41

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC126	NM_138771.4	c.217G>T	p.Gly73Cys	missense_variant	3/4	ENST00000307471.8	NP_620126.2
CCDC126	XM_017012775.3	c.217G>T	p.Gly73Cys	missense_variant	4/5		XP_016868264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC126	ENST00000307471.8	c.217G>T	p.Gly73Cys	missense_variant	3/4	1	NM_138771.4	ENSP00000304355	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Aug 03, 2022

The c.217G>T (p.G73C) alteration is located in exon 3 (coding exon 1) of the CCDC126 gene. This alteration results from a G to T substitution at nucleotide position 217, causing the glycine (G) at amino acid position 73 to be replaced by a cysteine (C). 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	Uncertain	0.54
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;T;T;T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.78	.;.;T;T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.61	D;D;D;D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	2.0	M;M;.;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.5	N;N;D;N
REVEL	Uncertain	0.39
Sift	Benign	0.044	D;D;T;D
Sift4G	Benign	0.067	T;T;T;T
Polyphen		1.0	D;D;.;D
Vest4		0.67
MutPred		0.31		Loss of disorder (P = 0.031);Loss of disorder (P = 0.031);Loss of disorder (P = 0.031);Loss of disorder (P = 0.031);
MVP		0.38
MPC		0.71
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.41
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr7-23651151; COSMIC: COSV56741458; COSMIC: COSV56741458;