rs757362220

Variant names:

• chr13-98177097-C-T
• rs757362220
• NM_178861.5:c.140G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_178861.5(RNF113B):​c.140G>A​(p.Ser47Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000537 in 1,600,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: RNF113B NM_178861.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.123
• Publications: 0 publications found

Genes affected

RNF113B (HGNC:17267): (ring finger protein 113B) Predicted to enable metal ion binding activity. Predicted to be involved in snoRNA splicing. Predicted to be part of U2-type spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

FARP1 (HGNC:3591): (FERM, ARH/RhoGEF and pleckstrin domain protein 1) This gene encodes a protein containing a FERM (4.2, exrin, radixin, moesin) domain, a Dbl homology domain, and two pleckstrin homology domains. These domains are found in guanine nucleotide exchange factors and proteins that link the cytoskeleton to the cell membrane. The encoded protein functions in neurons to promote dendritic growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016851395).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178861.5. 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
	RNF113B	NM_178861.5	MANE Select	c.140G>A	p.Ser47Asn	missense	Exon 1 of 2	NP_849192.1	Q8IZP6
	FARP1	NM_005766.4	MANE Select	c.-24+33605C>T		intron	N/A	NP_005757.1	A0A2X0TVY0
	FARP1	NM_001286839.2		c.-24+34320C>T		intron	N/A	NP_001273768.1	C9JME2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF113B	ENST00000267291.7	TSL:1 MANE Select	c.140G>A	p.Ser47Asn	missense	Exon 1 of 2	ENSP00000267291.6	Q8IZP6
	FARP1	ENST00000319562.11	TSL:1 MANE Select	c.-24+33605C>T		intron	N/A	ENSP00000322926.6	Q9Y4F1-1
	FARP1	ENST00000595437.5	TSL:1	c.-24+34320C>T		intron	N/A	ENSP00000471242.1	C9JME2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152142 Hom.: 0 Cov.: 31

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: 0.000831

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000157 AC: 37 AN: 236358 AF XY: 0.000193

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.0000566 AC: 82 AN: 1447878 Hom.: 0 Cov.: 34 AF XY: 0.0000805 AC XY: 58 AN XY: 720608

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

American (AMR) AF: 0.00 AC: 0 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.000894 AC: 77 AN: 86150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40982

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5196

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111544

Other (OTH) AF: 0.0000664 AC: 4 AN: 60202

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152142 Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3 AN XY: 74310

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.000831 AC: 4 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.000149 AC: 18

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

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	Benign	0.11
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.12
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.043
Sift	Benign	0.20	T
Sift4G	Benign	0.31	T
Polyphen		0.70	P
Vest4		0.15
MutPred		0.21		Loss of glycosylation at S47 (P = 0.0057)
MVP		0.34
MPC		0.44
ClinPred		0.042	T
GERP RS		0.26
PromoterAI		0.011	Neutral
Varity_R		0.075
gMVP		0.12
Mutation Taster		=95/5	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: rs757362220; hg19: chr13-98829351;