7-128801243-A-C

Position:

• chr7-128801243-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022742.5(CCDC136):​c.404A>C​(p.Glu135Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC136 NM_022742.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.36

Genes affected

CCDC136 (HGNC:22225): (coiled-coil domain containing 136) Predicted to be involved in acrosome assembly and single fertilization. Predicted to be integral component of membrane. Predicted to be active in acrosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

CCDC136 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35544503).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC136	NM_022742.5	c.404A>C	p.Glu135Ala	missense_variant	4/18	ENST00000297788.9	NP_073579.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC136	ENST00000297788.9	c.404A>C	p.Glu135Ala	missense_variant	4/18	1	NM_022742.5	ENSP00000297788.4

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

Mar 20, 2023

The c.404A>C (p.E135A) alteration is located in exon 4 (coding exon 4) of the CCDC136 gene. This alteration results from a A to C substitution at nucleotide position 404, causing the glutamic acid (E) at amino acid position 135 to be replaced by an alanine (A). 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	0.41
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.097	.;.;.;.;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.86	D;D;D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.36	T;T;T;T;T
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	2.0	.;.;.;.;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-4.5	D;D;D;D;D
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D;D
Polyphen		1.0	.;D;.;D;D
Vest4		0.66, 0.62, 0.54
MutPred		0.039		Gain of glycosylation at K137 (P = 0.1621);.;.;Gain of glycosylation at K137 (P = 0.1621);Gain of glycosylation at K137 (P = 0.1621);
MVP		0.70
MPC		0.48
ClinPred		0.98	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.37

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: chr7-128441297;