rs1440294029

Variant names:

• chr17-81667838-A-C
• rs1440294029
• NM_199287.3:c.244A>C

Your query was ambiguous. Multiple possible variants found:

• chr17-81667838-A-C
• chr17-81667838-A-G
• chr17-81667838-A-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.244A>C​(p.Ser82Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. S82G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CCDC137 NM_199287.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.803
• 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]

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=0.19841585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC137	NM_199287.3	c.244A>C	p.Ser82Arg	missense_variant	Exon 2 of 6	ENST00000329214.13	NP_954981.1
CCDC137	XM_047435910.1	c.34A>C	p.Ser12Arg	missense_variant	Exon 2 of 6		XP_047291866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC137	ENST00000329214.13	c.244A>C	p.Ser82Arg	missense_variant	Exon 2 of 6	1	NM_199287.3	ENSP00000329360.8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459630 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726100

African (AFR) AF: 0.0000299 AC: 1 AN: 33420

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4318

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111950

Other (OTH) AF: 0.00 AC: 0 AN: 60218

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.0030	T;T
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.22
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.74	.;T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.20	T;T
MetaSVM	Uncertain	0.64	D
MutationAssessor	Uncertain	2.6	M;.
PhyloP100		0.80
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.83	N;.
REVEL	Benign	0.29
Sift	Benign	0.31	T;.
Sift4G	Benign	0.37	T;T
Polyphen		1.0	D;.
Vest4		0.20
MutPred		0.24		Loss of phosphorylation at S82 (P = 0.024);Loss of phosphorylation at S82 (P = 0.024);
MVP		0.90
MPC		0.39
ClinPred		0.81	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1440294029; hg19: chr17-79634868;