chr17-81670337-C-G

Position:

• chr17-81670337-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199287.3(CCDC137):​c.381C>G​(p.His127Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,613,736 control chromosomes in the GnomAD database, including 38,089 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.24 (4833 hom., cov: 32)
  • Exomes 𝑓: 0.21 (33256 hom.)
• Consequence: CCDC137 NM_199287.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0041407943).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC137	NM_199287.3	c.381C>G	p.His127Gln	missense_variant	3/6	ENST00000329214.13	NP_954981.1
CCDC137	XM_047435910.1	c.171C>G	p.His57Gln	missense_variant	3/6		XP_047291866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC137	ENST00000329214.13	c.381C>G	p.His127Gln	missense_variant	3/6	1	NM_199287.3	ENSP00000329360	P1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36861 AN: 152056 Hom.: 4814 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.242

GnomAD3 exomes AF: 0.199 AC: 49523 AN: 248654 Hom.: 5258 AF XY: 0.196 AC XY: 26500 AN XY: 135124

Gnomad AFR exome AF: 0.354

Gnomad AMR exome AF: 0.132

Gnomad ASJ exome AF: 0.181

Gnomad EAS exome AF: 0.212

Gnomad SAS exome AF: 0.155

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.211

Gnomad OTH exome AF: 0.201

GnomAD4 exome AF: 0.210 AC: 306649 AN: 1461562 Hom.: 33256 Cov.: 39 AF XY: 0.207 AC XY: 150741 AN XY: 727052

Gnomad4 AFR exome AF: 0.365

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.258

Gnomad4 SAS exome AF: 0.153

Gnomad4 FIN exome AF: 0.195

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.243 AC: 36921 AN: 152174 Hom.: 4833 Cov.: 32 AF XY: 0.238 AC XY: 17709 AN XY: 74400

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.240

Alfa AF: 0.213 Hom.: 1153

Bravo AF: 0.250

TwinsUK AF: 0.212 AC: 785

ALSPAC AF: 0.213 AC: 820

ESP6500AA AF: 0.336 AC: 1319

ESP6500EA AF: 0.214 AC: 1782

ExAC AF: 0.204 AC: 24613

Asia WGS AF: 0.192 AC: 667 AN: 3478

EpiCase AF: 0.210

EpiControl AF: 0.215

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.1
DANN	Benign	0.63
DEOGEN2	Benign	0.00071	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0057	N
LIST_S2	Benign	0.21	.;T
MetaRNN	Benign	0.0041	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.5	N;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.1	N;.
REVEL	Benign	0.036
Sift	Benign	1.0	T;.
Sift4G	Benign	0.76	T;T
Polyphen		0.0	B;.
Vest4		0.022
MutPred		0.081		Gain of helix (P = 0.062);.;
MPC		0.060
ClinPred		0.00019	T
GERP RS		0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.019
gMVP		0.15

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

LitVar

Other links and lift over

dbSNP: rs7226091; hg19: chr17-79637367; COSMIC: COSV61303154; COSMIC: COSV61303154;