rs1393629863

Variant names:

• chr17-81666770-G-A
• rs1393629863
• NM_199287.3:c.4G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-81666770-G-A
• chr17-81666770-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_199287.3(CCDC137):​c.4G>A​(p.Ala2Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000228 in 1,316,832 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. A2S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: CCDC137 NM_199287.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33413455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC137	NM_199287.3	c.4G>A	p.Ala2Thr	missense_variant	Exon 1 of 6	ENST00000329214.13	NP_954981.1
OXLD1	NM_001039842.3	c.-193C>T		upstream_gene_variant		ENST00000374741.4	NP_001034931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC137	ENST00000329214.13	c.4G>A	p.Ala2Thr	missense_variant	Exon 1 of 6	1	NM_199287.3	ENSP00000329360.8
OXLD1	ENST00000374741.4	c.-193C>T		upstream_gene_variant		1	NM_001039842.3	ENSP00000363873.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000228 AC: 3 AN: 1316832 Hom.: 0 Cov.: 31 AF XY: 0.00000308 AC XY: 2 AN XY: 648932

African (AFR) AF: 0.00 AC: 0 AN: 26436

American (AMR) AF: 0.0000413 AC: 1 AN: 24186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19708

East Asian (EAS) AF: 0.00 AC: 0 AN: 31680

South Asian (SAS) AF: 0.0000148 AC: 1 AN: 67530

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4920

European-Non Finnish (NFE) AF: 9.55e-7 AC: 1 AN: 1047260

Other (OTH) AF: 0.00 AC: 0 AN: 53744

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0017	T;T
Eigen	Benign	0.065
Eigen_PC	Benign	-0.033
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.36	.;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;.
PhyloP100		2.3
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.87	N;.
REVEL	Benign	0.054
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.93	P;.
Vest4		0.26
MutPred		0.27		Gain of phosphorylation at A2 (P = 0.0783);Gain of phosphorylation at A2 (P = 0.0783);
MVP		0.38
MPC		0.058
ClinPred		0.93	D
GERP RS		3.0
PromoterAI		0.075	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1393629863; hg19: chr17-79633800;