13-98176963-C-T

Variant names:

• chr13-98176963-C-T
• rs16955011
• NM_178861.5:c.274G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178861.5(RNF113B):​c.274G>A​(p.Val92Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0658 in 1,600,954 control chromosomes in the GnomAD database, including 4,323 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.095 (928 hom., cov: 31)
  • Exomes 𝑓: 0.063 (3395 hom.)
• Consequence: RNF113B NM_178861.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.952
• Publications: 15 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012420118).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF113B	NM_178861.5	MANE Select	c.274G>A	p.Val92Met	missense	Exon 1 of 2	NP_849192.1
	FARP1	NM_005766.4	MANE Select	c.-24+33471C>T		intron	N/A	NP_005757.1
	FARP1	NM_001286839.2		c.-24+34186C>T		intron	N/A	NP_001273768.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF113B	ENST00000267291.7	TSL:1 MANE Select	c.274G>A	p.Val92Met	missense	Exon 1 of 2	ENSP00000267291.6
	FARP1	ENST00000319562.11	TSL:1 MANE Select	c.-24+33471C>T		intron	N/A	ENSP00000322926.6
	FARP1	ENST00000595437.5	TSL:1	c.-24+34186C>T		intron	N/A	ENSP00000471242.1

Frequencies

GnomAD3 genomes AF: 0.0953 AC: 14474 AN: 151856 Hom.: 924 Cov.: 31

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.0641

Gnomad SAS AF: 0.0770

Gnomad FIN AF: 0.0380

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0570

Gnomad OTH AF: 0.0898

GnomAD2 exomes AF: 0.0766 AC: 18337 AN: 239378 AF XY: 0.0724

Gnomad AFR exome AF: 0.171

Gnomad AMR exome AF: 0.126

Gnomad ASJ exome AF: 0.0506

Gnomad EAS exome AF: 0.0552

Gnomad FIN exome AF: 0.0432

Gnomad NFE exome AF: 0.0585

Gnomad OTH exome AF: 0.0684

GnomAD4 exome AF: 0.0627 AC: 90787 AN: 1448980 Hom.: 3395 Cov.: 35 AF XY: 0.0623 AC XY: 44944 AN XY: 721292

African (AFR) AF: 0.172 AC: 5746 AN: 33472

American (AMR) AF: 0.125 AC: 5580 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 1219 AN: 26110

East Asian (EAS) AF: 0.0892 AC: 3542 AN: 39692

South Asian (SAS) AF: 0.0700 AC: 6034 AN: 86246

European-Finnish (FIN) AF: 0.0413 AC: 1684 AN: 40812

Middle Eastern (MID) AF: 0.0590 AC: 340 AN: 5766

European-Non Finnish (NFE) AF: 0.0565 AC: 62768 AN: 1111858

Other (OTH) AF: 0.0642 AC: 3874 AN: 60316

GnomAD4 genome AF: 0.0954 AC: 14502 AN: 151974 Hom.: 928 Cov.: 31 AF XY: 0.0960 AC XY: 7131 AN XY: 74292

African (AFR) AF: 0.170 AC: 7055 AN: 41430

American (AMR) AF: 0.135 AC: 2062 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0438 AC: 152 AN: 3468

East Asian (EAS) AF: 0.0643 AC: 329 AN: 5120

South Asian (SAS) AF: 0.0768 AC: 369 AN: 4804

European-Finnish (FIN) AF: 0.0380 AC: 403 AN: 10604

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.0570 AC: 3873 AN: 67962

Other (OTH) AF: 0.0913 AC: 192 AN: 2104

Alfa AF: 0.0706 Hom.: 1737

Bravo AF: 0.106

TwinsUK AF: 0.0588 AC: 218

ALSPAC AF: 0.0592 AC: 228

ESP6500AA AF: 0.160 AC: 703

ESP6500EA AF: 0.0578 AC: 497

ExAC AF: 0.0744 AC: 9026

Asia WGS AF: 0.0840 AC: 290 AN: 3478

EpiCase AF: 0.0590

EpiControl AF: 0.0636

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		0.95
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.15
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.014	D
Polyphen		0.98	D
Vest4		0.018
MPC		0.51
ClinPred		0.055	T
GERP RS		0.21
PromoterAI		0.039	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.73
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs16955011; hg19: chr13-98829217; COSMIC: COSV57434265; COSMIC: COSV57434265;