NM_032905.5:c.1004A>C

Variant names:

• chr10-6114122-A-C
• rs775801085
• NM_032905.5:c.1004A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032905.5(RBM17):​c.1004A>C​(p.Lys335Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,708 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RBM17 NM_032905.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.03

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM17	NM_032905.5	c.1004A>C	p.Lys335Thr	missense_variant	Exon 10 of 12	ENST00000379888.9	NP_116294.1
RBM17	NM_001145547.2	c.1004A>C	p.Lys335Thr	missense_variant	Exon 10 of 12		NP_001139019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM17	ENST00000379888.9	c.1004A>C	p.Lys335Thr	missense_variant	Exon 10 of 12	1	NM_032905.5	ENSP00000369218.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250762 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135538

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458708 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 725832

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	.;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.040	N;N
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-2.0	N;N
REVEL	Uncertain	0.61
Sift	Uncertain	0.016	D;D
Sift4G	Uncertain	0.023	D;D
Polyphen		0.88	P;P
Vest4		0.66
MutPred		0.60		Loss of methylation at K335 (P = 0.0084);Loss of methylation at K335 (P = 0.0084);
MVP		0.51
MPC		3.5
ClinPred		0.86	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs775801085; hg19: chr10-6156085;