17-81672517-T-G

Position:

• chr17-81672517-T-G

Variant summary

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

The ENST00000329214.13(CCDC137):​c.683T>G​(p.Leu228Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC137 ENST00000329214.13 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.42

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC137	NM_199287.3	c.683T>G	p.Leu228Arg	missense_variant	6/6	ENST00000329214.13	NP_954981.1
CCDC137	XM_047435910.1	c.473T>G	p.Leu158Arg	missense_variant	6/6		XP_047291866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC137	ENST00000329214.13	c.683T>G	p.Leu228Arg	missense_variant	6/6	1	NM_199287.3	ENSP00000329360	P1
CCDC137	ENST00000574107.1	c.710T>G	p.Leu237Arg	missense_variant	7/7	3		ENSP00000458350
CCDC137	ENST00000575223.5	c.683T>G	p.Leu228Arg	missense_variant, NMD_transcript_variant	6/7	5		ENSP00000458884
CCDC137	ENST00000571916.1	c.*318T>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	3		ENSP00000460261

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Feb 10, 2023

The c.683T>G (p.L228R) alteration is located in exon 6 (coding exon 6) of the CCDC137 gene. This alteration results from a T to G substitution at nucleotide position 683, causing the leucine (L) at amino acid position 228 to be replaced by an arginine (R). 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	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.69	.;T
M_CAP	Pathogenic	0.32	D
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	3.3	M;.
MutationTaster	Benign	0.55	D
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-5.1	D;.
REVEL	Uncertain	0.57
Sift	Uncertain	0.0050	D;.
Sift4G	Benign	0.21	T;T
Polyphen		1.0	D;.
Vest4		0.89
MutPred		0.35		Gain of methylation at L228 (P = 0.0334);.;
MVP		0.91
MPC		0.43
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.64
gMVP		0.56

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: chr17-79639547;