NM_199287.3:c.381C>G

Variant names:

• chr17-81670337-C-G
• rs7226091
• NM_199287.3:c.381C>G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 28 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199287.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC137	NM_199287.3	MANE Select	c.381C>G	p.His127Gln	missense	Exon 3 of 6	NP_954981.1	Q6PK04

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC137	ENST00000329214.13	TSL:1 MANE Select	c.381C>G	p.His127Gln	missense	Exon 3 of 6	ENSP00000329360.8	Q6PK04
	CCDC137	ENST00000574107.1	TSL:3	c.408C>G	p.His136Gln	missense	Exon 4 of 7	ENSP00000458350.1	I3L0U5
	CCDC137	ENST00000571916.1	TSL:3	n.*16C>G		non_coding_transcript_exon	Exon 2 of 5	ENSP00000460261.1	I3L385

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

GnomAD2 exomes AF: 0.199 AC: 49523 AN: 248654 AF XY: 0.196

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 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

African (AFR) AF: 0.365 AC: 12233 AN: 33480

American (AMR) AF: 0.138 AC: 6170 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 4818 AN: 26136

East Asian (EAS) AF: 0.258 AC: 10241 AN: 39694

South Asian (SAS) AF: 0.153 AC: 13189 AN: 86254

European-Finnish (FIN) AF: 0.195 AC: 10383 AN: 53224

Middle Eastern (MID) AF: 0.237 AC: 1364 AN: 5766

European-Non Finnish (NFE) AF: 0.211 AC: 235073 AN: 1111914

Other (OTH) AF: 0.218 AC: 13178 AN: 60386

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

African (AFR) AF: 0.350 AC: 14534 AN: 41478

American (AMR) AF: 0.189 AC: 2889 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 639 AN: 3472

East Asian (EAS) AF: 0.216 AC: 1118 AN: 5172

South Asian (SAS) AF: 0.155 AC: 749 AN: 4820

European-Finnish (FIN) AF: 0.189 AC: 2004 AN: 10598

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14181 AN: 68020

Other (OTH) AF: 0.240 AC: 506 AN: 2112

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 v4.9

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
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
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.5	N
PhyloP100		0.13
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.036
Sift	Benign	1.0	T
Sift4G	Benign	0.76	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
Mutation Taster		=95/5	polymorphism (auto)

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