7-23611521-A-T

Position:

• chr7-23611521-A-T

Variant summary

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

The NM_138771.4(CCDC126):​c.206A>T​(p.Asp69Val) variant causes a missense change. 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: 4.77

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.206A>T	p.Asp69Val	missense_variant	3/4	ENST00000307471.8	NP_620126.2
CCDC126	XM_017012775.3	c.206A>T	p.Asp69Val	missense_variant	4/5		XP_016868264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC126	ENST00000307471.8	c.206A>T	p.Asp69Val	missense_variant	3/4	1	NM_138771.4	ENSP00000304355	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2023

The c.206A>T (p.D69V) alteration is located in exon 3 (coding exon 1) of the CCDC126 gene. This alteration results from a A to T substitution at nucleotide position 206, causing the aspartic acid (D) at amino acid position 69 to be replaced by a valine (V). 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	0.16
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;T;T;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.70	.;.;T;T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.48	T;T;T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.8	L;L;.;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-5.7	D;D;D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		0.91	P;P;.;P
Vest4		0.35
MutPred		0.39		Gain of sheet (P = 0.0043);Gain of sheet (P = 0.0043);Gain of sheet (P = 0.0043);Gain of sheet (P = 0.0043);
MVP		0.18
MPC		0.74
ClinPred		0.97	D
GERP RS		5.7
Varity_R		0.54
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr7-23651140;