chr17-81667771-C-G

Variant names:

• chr17-81667771-C-G
• rs1568199699
• NM_199287.3:c.177C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_199287.3(CCDC137):​c.177C>G​(p.Asp59Glu) 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 NM_199287.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.02
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17321101).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC137	NM_199287.3	c.177C>G	p.Asp59Glu	missense_variant	Exon 2 of 6	ENST00000329214.13	NP_954981.1
CCDC137	XM_047435910.1	c.-34C>G		5_prime_UTR_variant	Exon 2 of 6		XP_047291866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC137	ENST00000329214.13	c.177C>G	p.Asp59Glu	missense_variant	Exon 2 of 6	1	NM_199287.3	ENSP00000329360.8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.177C>G (p.D59E) alteration is located in exon 2 (coding exon 2) of the CCDC137 gene. This alteration results from a C to G substitution at nucleotide position 177, causing the aspartic acid (D) at amino acid position 59 to be replaced by a glutamic acid (E). 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	0.32
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	11
DANN	Benign	0.85
DEOGEN2	Benign	0.046	T;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.59	.;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Uncertain	0.19	D
MutationAssessor	Uncertain	2.5	M;.
PhyloP100		-2.0
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.1	N;.
REVEL	Uncertain	0.40
Sift	Benign	0.14	T;.
Sift4G	Benign	0.54	T;T
Polyphen		0.99	D;.
Vest4		0.29
MutPred		0.36		Loss of MoRF binding (P = 0.1155);Loss of MoRF binding (P = 0.1155);
MVP		0.76
MPC		0.37
ClinPred		0.82	D
GERP RS		-4.7
Varity_R		0.11
gMVP		0.29

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

Other links and lift over

dbSNP: rs1568199699; hg19: chr17-79634801;