chr17-81670323-G-C

Variant names:

• chr17-81670323-G-C
• rs199850384
• NM_199287.3:c.367G>C

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.367G>C​(p.Gly123Arg) 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. 16/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC137 NM_199287.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 5 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=0.027120411).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC137	NM_199287.3	c.367G>C	p.Gly123Arg	missense_variant	Exon 3 of 6	ENST00000329214.13	NP_954981.1
CCDC137	XM_047435910.1	c.157G>C	p.Gly53Arg	missense_variant	Exon 3 of 6		XP_047291866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC137	ENST00000329214.13	c.367G>C	p.Gly123Arg	missense_variant	Exon 3 of 6	1	NM_199287.3	ENSP00000329360.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248816 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.0060
DANN	Benign	0.44
DEOGEN2	Benign	0.0013	T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.68	.;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.027	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.23	N;.
PhyloP100		-2.3
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.30	N;.
REVEL	Benign	0.032
Sift	Benign	0.68	T;.
Sift4G	Benign	0.80	T;T
Polyphen		0.0050	B;.
Vest4		0.090
MutPred		0.17		Gain of MoRF binding (P = 0.0234);.;
MVP		0.030
MPC		0.073
ClinPred		0.021	T
GERP RS		-7.9
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.028
gMVP		0.16

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

Other links and lift over

dbSNP: rs199850384; hg19: chr17-79637353;