13-98176966-C-G

Variant names:

• chr13-98176966-C-G
• rs540055745
• NM_178861.5:c.271G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178861.5(RNF113B):​c.271G>C​(p.Asp91His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,600,756 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. 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. D91N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RNF113B NM_178861.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• Publications: 1 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057489395).

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.271G>C	p.Asp91His	missense	Exon 1 of 2	NP_849192.1	Q8IZP6
	FARP1	NM_005766.4	MANE Select	c.-24+33474C>G		intron	N/A	NP_005757.1	A0A2X0TVY0
	FARP1	NM_001286839.2		c.-24+34189C>G		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.271G>C	p.Asp91His	missense	Exon 1 of 2	ENSP00000267291.6	Q8IZP6
	FARP1	ENST00000319562.11	TSL:1 MANE Select	c.-24+33474C>G		intron	N/A	ENSP00000322926.6	Q9Y4F1-1
	FARP1	ENST00000595437.5	TSL:1	c.-24+34189C>G		intron	N/A	ENSP00000471242.1	C9JME2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151938 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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448818 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 721214

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40662

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111854

Other (OTH) AF: 0.0000166 AC: 1 AN: 60316

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151938 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74202

African (AFR) AF: 0.00 AC: 0 AN: 41372

American (AMR) AF: 0.00 AC: 0 AN: 15266

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67974

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.79
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.24
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.027
Sift	Benign	0.055	T
Sift4G	Benign	0.14	T
Polyphen		0.024	B
Vest4		0.046
MutPred		0.25		Gain of sheet (P = 0.0477)
MVP		0.13
MPC		0.56
ClinPred		0.073	T
GERP RS		1.2
PromoterAI		-0.12	Neutral
Varity_R		0.060
gMVP		0.45
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs540055745; hg19: chr13-98829220;