chr7-128794446-A-G

Position:

• chr7-128794446-A-G

Variant summary

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

The NM_022742.5(CCDC136):​c.115A>G​(p.Ser39Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000428 in 1,400,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: CCDC136 NM_022742.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.719

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=0.07814774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC136	NM_022742.5	c.115A>G	p.Ser39Gly	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.115A>G	p.Ser39Gly	missense_variant	2/18	1	NM_022742.5	ENSP00000297788	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000428 AC: 6 AN: 1400332 Hom.: 0 Cov.: 32 AF XY: 0.00000290 AC XY: 2 AN XY: 690698

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000556

Gnomad4 OTH exome AF: 0.00

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

Dec 21, 2022

The c.115A>G (p.S39G) alteration is located in exon 2 (coding exon 2) of the CCDC136 gene. This alteration results from a A to G substitution at nucleotide position 115, causing the serine (S) at amino acid position 39 to be replaced by a glycine (G). 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	0.068
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	.;T;.;.;T;.;T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.70	T;T;T;T;T;T;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.078	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	.;.;.;.;.;.;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.6	N;N;N;N;D;N;N
REVEL	Benign	0.016
Sift	Benign	0.035	D;D;D;D;D;D;D
Sift4G	Benign	0.20	T;T;T;T;T;T;T
Polyphen		0.0010, 0.0040	.;.;B;.;.;B;B
Vest4		0.15, 0.18, 0.16, 0.12
MVP		0.12
MPC		0.084
ClinPred		0.050	T
GERP RS		2.0
Varity_R		0.064
gMVP		0.092

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr7-128434500;