chr2-160367366-A-T

Variant names:

• chr2-160367366-A-T
• rs759673460
• ENST00000409075.5:c.2T>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PVS1_Supporting

The ENST00000409075.5(RBMS1):​c.2T>A​(p.Met1?) variant causes a start lost change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00078 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0097 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RBMS1 ENST00000409075.5 start_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 99 codons. Genomic position: 160313164. Lost 0.265 part of the original CDS.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000409075.5. 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.101T>A	p.Met34Lys	missense	Exon 2 of 14	NP_058520.1	P29558-1
	RBMS1	NM_002897.5		c.101T>A	p.Met34Lys	missense	Exon 2 of 14	NP_002888.1	A0A0S2Z499

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBMS1	ENST00000409075.5	TSL:1	c.2T>A	p.Met1?	start_lost	Exon 2 of 14	ENSP00000386347.1	E7ETU5
	RBMS1	ENST00000348849.8	TSL:1 MANE Select	c.101T>A	p.Met34Lys	missense	Exon 2 of 14	ENSP00000294904.6	P29558-1
	RBMS1	ENST00000474820.5	TSL:1	n.227T>A		non_coding_transcript_exon	Exon 3 of 16

Frequencies

GnomAD3 genomes AF: 0.000775 AC: 113 AN: 145740 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000743

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00476

Gnomad SAS AF: 0.00535

Gnomad FIN AF: 0.00107

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000227

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00965 AC: 11262 AN: 1166634 Hom.: 0 Cov.: 32 AF XY: 0.00962 AC XY: 5616 AN XY: 583664

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

African (AFR) AF: 0.0173 AC: 460 AN: 26586

American (AMR) AF: 0.00926 AC: 365 AN: 39408

Ashkenazi Jewish (ASJ) AF: 0.0261 AC: 501 AN: 19178

East Asian (EAS) AF: 0.0319 AC: 754 AN: 23656

South Asian (SAS) AF: 0.00216 AC: 177 AN: 81818

European-Finnish (FIN) AF: 0.0147 AC: 551 AN: 37608

Middle Eastern (MID) AF: 0.0143 AC: 67 AN: 4700

European-Non Finnish (NFE) AF: 0.00850 AC: 7551 AN: 888618

Other (OTH) AF: 0.0186 AC: 836 AN: 45062

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000782 AC: 114 AN: 145868 Hom.: 0 Cov.: 32 AF XY: 0.000801 AC XY: 57 AN XY: 71140

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

African (AFR) AF: 0.000791 AC: 32 AN: 40450

American (AMR) AF: 0.00102 AC: 15 AN: 14778

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3396

East Asian (EAS) AF: 0.00476 AC: 21 AN: 4412

South Asian (SAS) AF: 0.00510 AC: 21 AN: 4116

European-Finnish (FIN) AF: 0.00107 AC: 10 AN: 9368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.000227 AC: 15 AN: 66132

Other (OTH) AF: 0.00 AC: 0 AN: 2062

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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	0.71
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.50	D
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		9.3
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.29
Sift	Uncertain	0.028	D
Sift4G	Benign	0.18	T
Polyphen		0.44	B
Vest4		0.72
MutPred		0.41		Gain of solvent accessibility (P = 4e-04)
MVP		0.47
MPC		0.76
ClinPred		0.95	D
GERP RS		5.6
Varity_R		0.69
gMVP		0.78
Mutation Taster		=27/173	disease causing

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: rs759673460; hg19: chr2-161223877;