rs1175397389

Variant names:

• chr17-81666882-C-G
• rs1175397389
• NM_199287.3:c.116C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-81666882-C-G
• chr17-81666882-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_199287.3(CCDC137):​c.116C>G​(p.Pro39Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000177 in 1,132,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P39L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: CCDC137 NM_199287.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366
• Publications: 0 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]

OXLD1 (HGNC:27901): (oxidoreductase like domain containing 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2430515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC137	NM_199287.3	c.116C>G	p.Pro39Arg	missense_variant	Exon 1 of 6	ENST00000329214.13	NP_954981.1
CCDC137	XM_047435910.1	c.-202C>G		5_prime_UTR_variant	Exon 1 of 6		XP_047291866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC137	ENST00000329214.13	c.116C>G	p.Pro39Arg	missense_variant	Exon 1 of 6	1	NM_199287.3	ENSP00000329360.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000177 AC: 2 AN: 1132932 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 542246

African (AFR) AF: 0.00 AC: 0 AN: 23194

American (AMR) AF: 0.00 AC: 0 AN: 8736

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15208

East Asian (EAS) AF: 0.00 AC: 0 AN: 26730

South Asian (SAS) AF: 0.0000273 AC: 1 AN: 36666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26740

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3046

European-Non Finnish (NFE) AF: 0.00000106 AC: 1 AN: 946942

Other (OTH) AF: 0.00 AC: 0 AN: 45670

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.0046	T;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.63	.;T
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Uncertain	2.4	M;.
PhyloP100		0.37
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.9	N;.
REVEL	Benign	0.26
Sift	Uncertain	0.0050	D;.
Sift4G	Uncertain	0.010	D;D
Polyphen		0.96	D;.
Vest4		0.33
MutPred		0.32		Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);
MVP		0.81
MPC		0.33
ClinPred		0.80	D
GERP RS		1.3
PromoterAI		-0.020	Neutral
Varity_R		0.069
gMVP		0.11
Mutation Taster		=100/0	polymorphism

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: rs1175397389; hg19: chr17-79633912;