NM_032905.5:c.307A>C

Variant names:

• chr10-6104997-A-C
• rs753474883
• NM_032905.5:c.307A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032905.5(RBM17):​c.307A>C​(p.Met103Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: RBM17 NM_032905.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.78

Genes affected

RBM17 (HGNC:16944): (RNA binding motif protein 17) This gene encodes an RNA binding protein. The encoded protein is part of the spliceosome complex and functions in the second catalytic step of mRNA splicing. Alternatively spliced transcript variants have been described. Related pseudogenes exist on chromosomes 9 and 15. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26783657).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM17	NM_032905.5	c.307A>C	p.Met103Leu	missense_variant	Exon 4 of 12	ENST00000379888.9	NP_116294.1
RBM17	NM_001145547.2	c.307A>C	p.Met103Leu	missense_variant	Exon 4 of 12		NP_001139019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM17	ENST00000379888.9	c.307A>C	p.Met103Leu	missense_variant	Exon 4 of 12	1	NM_032905.5	ENSP00000369218.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461708 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727174

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.078	T;.;T;T;T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.098
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	.;D;D;D;D
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.27	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;.;.;L;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.040	N;N;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.61	T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.020	B;.;.;B;.
Vest4		0.79
MutPred		0.28		Gain of catalytic residue at M103 (P = 0.008);.;Gain of catalytic residue at M103 (P = 0.008);Gain of catalytic residue at M103 (P = 0.008);Gain of catalytic residue at M103 (P = 0.008);
MVP		0.76
MPC		1.6
ClinPred		0.78	D
GERP RS		5.4
Varity_R		0.29
gMVP		0.42

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: rs753474883; hg19: chr10-6146960;