7-23643101-G-A

Position:

• chr7-23643101-G-A

Variant summary

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

The NM_138771.4(CCDC126):​c.409G>A​(p.Gly137Ser) 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. 12/20 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: 4.09

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=0.08641279).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC126	NM_138771.4	c.409G>A	p.Gly137Ser	missense_variant	4/4	ENST00000307471.8	NP_620126.2
CCDC126	XM_017012775.3	c.409G>A	p.Gly137Ser	missense_variant	5/5		XP_016868264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC126	ENST00000307471.8	c.409G>A	p.Gly137Ser	missense_variant	4/4	1	NM_138771.4	ENSP00000304355	P1
CCDC126	ENST00000409765.5	c.409G>A	p.Gly137Ser	missense_variant	3/3	1		ENSP00000386675	P1
CCDC126	ENST00000410069.1	c.409G>A	p.Gly137Ser	missense_variant	4/4	1		ENSP00000386355	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Mar 29, 2023

The c.409G>A (p.G137S) alteration is located in exon 4 (coding exon 2) of the CCDC126 gene. This alteration results from a G to A substitution at nucleotide position 409, causing the glycine (G) at amino acid position 137 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	0.071
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0099	T;T;T
Eigen	Benign	0.052
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.58	.;.;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.086	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.8	L;L;L
MutationTaster	Benign	0.95	D;D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.52	N;N;N
REVEL	Uncertain	0.29
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.29	B;B;B
Vest4		0.12
MutPred		0.24		Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP		0.095
MPC		0.18
ClinPred		0.50	T
GERP RS		5.8
Varity_R		0.044
gMVP		0.43

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: chr7-23682720;