17-81667838-A-G

Position:

• chr17-81667838-A-G

Variant summary

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

The ENST00000329214.13(CCDC137):​c.244A>G​(p.Ser82Gly) 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: 31)
• Consequence: CCDC137 ENST00000329214.13 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.803

Genes affected

CCDC137 (HGNC:33451): (coiled-coil domain containing 137) Enables RNA binding activity. Located in chromosome and fibrillar center. [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=0.19741762).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC137	NM_199287.3	c.244A>G	p.Ser82Gly	missense_variant	2/6	ENST00000329214.13	NP_954981.1
CCDC137	XM_047435910.1	c.34A>G	p.Ser12Gly	missense_variant	2/6		XP_047291866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC137	ENST00000329214.13	c.244A>G	p.Ser82Gly	missense_variant	2/6	1	NM_199287.3	ENSP00000329360	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000302

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

Apr 09, 2024

The c.244A>G (p.S82G) alteration is located in exon 2 (coding exon 2) of the CCDC137 gene. This alteration results from a A to G substitution at nucleotide position 244, causing the serine (S) at amino acid position 82 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	0.14
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Benign	0.86
DEOGEN2	Benign	0.0028	T;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.55	.;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.20	T;T
MetaSVM	Uncertain	0.49	D
MutationAssessor	Pathogenic	2.9	M;.
MutationTaster	Benign	0.66	N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.1	N;.
REVEL	Uncertain	0.30
Sift	Benign	0.27	T;.
Sift4G	Benign	0.27	T;T
Polyphen		1.0	D;.
Vest4		0.11
MutPred		0.21		Loss of stability (P = 0.0161);Loss of stability (P = 0.0161);
MVP		0.90
MPC		0.10
ClinPred		0.85	D
GERP RS		4.3
Varity_R		0.096
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1440294029; hg19: chr17-79634868;