17-81670386-G-A

Position:

• chr17-81670386-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_199287.3(CCDC137):​c.430G>A​(p.Ala144Thr) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC137 NM_199287.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.876

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052001).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC137	NM_199287.3	c.430G>A	p.Ala144Thr	missense_variant	3/6	ENST00000329214.13	NP_954981.1
CCDC137	XM_047435910.1	c.220G>A	p.Ala74Thr	missense_variant	3/6		XP_047291866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC137	ENST00000329214.13	c.430G>A	p.Ala144Thr	missense_variant	3/6	1	NM_199287.3	ENSP00000329360	P1
CCDC137	ENST00000574107.1	c.457G>A	p.Ala153Thr	missense_variant	4/7	3		ENSP00000458350
CCDC137	ENST00000575223.5	c.430G>A	p.Ala144Thr	missense_variant, NMD_transcript_variant	3/7	5		ENSP00000458884
CCDC137	ENST00000571916.1	c.*65G>A		3_prime_UTR_variant, NMD_transcript_variant	2/5	3		ENSP00000460261

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

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

Aug 08, 2022

The c.430G>A (p.A144T) alteration is located in exon 3 (coding exon 3) of the CCDC137 gene. This alteration results from a G to A substitution at nucleotide position 430, causing the alanine (A) at amino acid position 144 to be replaced by a threonine (T). 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	0.084
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.0020	T;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.62	.;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.052	T;T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.85	N;.
REVEL	Benign	0.11
Sift	Benign	0.28	T;.
Sift4G	Benign	0.30	T;T
Polyphen		0.015	B;.
Vest4		0.055
MutPred		0.21		Gain of loop (P = 0.0312);.;
MVP		0.80
MPC		0.096
ClinPred		0.098	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.038
gMVP		0.20

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: chr17-79637416;