NM_199287.3:c.685C>G

Variant names:

• chr17-81672519-C-G
• rs371084134
• NM_199287.3:c.685C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_199287.3(CCDC137):​c.685C>G​(p.Arg229Gly) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R229W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC137 NM_199287.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051158756).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC137	NM_199287.3	c.685C>G	p.Arg229Gly	missense_variant	Exon 6 of 6	ENST00000329214.13	NP_954981.1
CCDC137	XM_047435910.1	c.475C>G	p.Arg159Gly	missense_variant	Exon 6 of 6		XP_047291866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC137	ENST00000329214.13	c.685C>G	p.Arg229Gly	missense_variant	Exon 6 of 6	1	NM_199287.3	ENSP00000329360.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	11
DANN	Benign	0.61
DEOGEN2	Benign	0.0065	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.55	.;T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.2	L;.
PhyloP100		1.4
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.5	D;.
REVEL	Benign	0.17
Sift	Benign	0.26	T;.
Sift4G	Benign	0.36	T;T
Polyphen		0.0040	B;.
Vest4		0.033
MutPred		0.16		Loss of MoRF binding (P = 0.0094);.;
MVP		0.57
MPC		0.078
ClinPred		0.084	T
GERP RS		3.8
Varity_R		0.099
gMVP		0.098

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs371084134; hg19: chr17-79639549;