NM_018989.2:c.1000C>G

Variant names:

• chr5-146233599-C-G
• rs768529948
• NM_018989.2:c.1000C>G

Variant summary

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

The NM_018989.2(RBM27):​c.1000C>G​(p.Pro334Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. P334S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RBM27 NM_018989.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.03
• Publications: 0 publications found

Genes affected

RBM27 (HGNC:29243): (RNA binding motif protein 27) Enables RNA binding activity. Predicted to be involved in mRNA processing. Predicted to be located in cytoplasm and nuclear speck. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000275740 (HGNC:58349):

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=0.24871182).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018989.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM27	NM_018989.2	MANE Select	c.1000C>G	p.Pro334Ala	missense	Exon 7 of 21	NP_061862.1	Q9P2N5
	RBM27-POU4F3	NM_001414499.1		c.1000C>G	p.Pro334Ala	missense	Exon 7 of 20	NP_001401428.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM27	ENST00000265271.7	TSL:1 MANE Select	c.1000C>G	p.Pro334Ala	missense	Exon 7 of 21	ENSP00000265271.5	Q9P2N5
	ENSG00000275740	ENST00000506502.2	TSL:5	c.1000C>G	p.Pro334Ala	missense	Exon 7 of 20	ENSP00000475384.1	U3KPZ7
	RBM27	ENST00000861565.1		c.1003C>G	p.Pro335Ala	missense	Exon 7 of 21	ENSP00000531624.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459604 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726282

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.00 AC: 0 AN: 86140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110234

Other (OTH) AF: 0.00 AC: 0 AN: 60288

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.073
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.0
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.12
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.060	T
Polyphen		0.0090	B
Vest4		0.54
MutPred		0.40		Loss of glycosylation at P334 (P = 0.0079)
MVP		0.41
MPC		0.31
ClinPred		0.63	D
GERP RS		5.6
Varity_R		0.21
gMVP		0.55
Mutation Taster		=61/39	polymorphism

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: rs768529948; hg19: chr5-145613162;