chr7-128794389-G-C

Position:

• chr7-128794389-G-C

Variant summary

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

The NM_022742.5(CCDC136):​c.58G>C​(p.Glu20Gln) variant causes a missense change involving the alteration of a non-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: 3.17

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]

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=0.16594222).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC136	NM_022742.5	c.58G>C	p.Glu20Gln	missense_variant	2/18	ENST00000297788.9	NP_073579.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC136	ENST00000297788.9	c.58G>C	p.Glu20Gln	missense_variant	2/18	1	NM_022742.5	ENSP00000297788	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Nov 15, 2021

The c.58G>C (p.E20Q) alteration is located in exon 2 (coding exon 2) of the CCDC136 gene. This alteration results from a G to C substitution at nucleotide position 58, causing the glutamic acid (E) at amino acid position 20 to be replaced by a glutamine (Q). 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	0.35
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	.;T;.;.;T;.;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.90	D;D;D;D;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.17	T;T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.4	.;.;.;.;.;.;L
MutationTaster	Benign	0.56	D;N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.3	N;N;N;N;D;N;N
REVEL	Benign	0.095
Sift	Pathogenic	0.0	D;D;D;D;D;D;D
Sift4G	Uncertain	0.027	D;D;T;D;D;D;D
Polyphen		0.99, 1.0, 1.0	.;.;D;.;.;D;D
Vest4		0.28, 0.27, 0.29, 0.28
MutPred		0.13		Loss of helix (P = 0.5774);Loss of helix (P = 0.5774);.;.;Loss of helix (P = 0.5774);Loss of helix (P = 0.5774);Loss of helix (P = 0.5774);
MVP		0.54
MPC		0.46
ClinPred		0.92	D
GERP RS		4.2
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		3.8
Varity_R		0.32
gMVP		0.22

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: chr7-128434443;