2-160278553-C-T

Variant names:

• chr2-160278553-C-T
• rs927210621
• NM_016836.4:c.1057G>A

Variant summary

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

The NM_016836.4(RBMS1):​c.1057G>A​(p.Gly353Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000807 in 1,611,194 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: RBMS1 NM_016836.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.87
• Publications: 1 publications found

Genes affected

RBMS1 (HGNC:9907): (RNA binding motif single stranded interacting protein 1) This gene encodes a member of a small family of proteins which bind single stranded DNA/RNA. These proteins are characterized by the presence of two sets of ribonucleoprotein consensus sequence (RNP-CS) that contain conserved motifs, RNP1 and RNP2, originally described in RNA binding proteins, and required for DNA binding. These proteins have been implicated in such diverse functions as DNA replication, gene transcription, cell cycle progression and apoptosis. Several transcript variants, resulting from alternative splicing and encoding different isoforms, have been described. A pseudogene for this locus is found on chromosome 12. [provided by RefSeq, Feb 2009]

ENSG00000300196 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016836.4. 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
	RBMS1	NM_016836.4	MANE Select	c.1057G>A	p.Gly353Arg	missense	Exon 11 of 14	NP_058520.1	P29558-1
	RBMS1	NM_002897.5		c.1048G>A	p.Gly350Arg	missense	Exon 11 of 14	NP_002888.1	A0A0S2Z499

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBMS1	ENST00000348849.8	TSL:1 MANE Select	c.1057G>A	p.Gly353Arg	missense	Exon 11 of 14	ENSP00000294904.6	P29558-1
	RBMS1	ENST00000409075.5	TSL:1	c.949G>A	p.Gly317Arg	missense	Exon 11 of 14	ENSP00000386347.1	E7ETU5
	RBMS1	ENST00000474820.5	TSL:1	n.1231G>A		non_coding_transcript_exon	Exon 13 of 16

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152070 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250592 AF XY: 0.00000738

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 FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000754 AC: 11 AN: 1459124 Hom.: 0 Cov.: 30 AF XY: 0.00000826 AC XY: 6 AN XY: 726024

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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

American (AMR) AF: 0.00 AC: 0 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86138

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 0.00000721 AC: 8 AN: 1109914

Other (OTH) AF: 0.00 AC: 0 AN: 60268

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000410614), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152070 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74282

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.61	D
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.9
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.93
MVP		0.45
MPC		1.3
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.61
gMVP		0.77
Mutation Taster		=54/46	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: rs927210621; hg19: chr2-161135064;