13-98176922-T-G

Variant names:

• chr13-98176922-T-G
• rs628778
• NM_178861.5:c.315A>C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_178861.5(RNF113B):​c.315A>C​(p.Pro105Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RNF113B NM_178861.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.06

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

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-3.06 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF113B	NM_178861.5	c.315A>C	p.Pro105Pro	synonymous_variant	Exon 1 of 2	ENST00000267291.7	NP_849192.1
FARP1	NM_005766.4	c.-24+33430T>G		intron_variant	Intron 1 of 26	ENST00000319562.11	NP_005757.1
FARP1	NM_001286839.2	c.-24+34145T>G		intron_variant	Intron 1 of 27		NP_001273768.1
FARP1	NM_001001715.4	c.-24+33430T>G		intron_variant	Intron 1 of 2		NP_001001715.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF113B	ENST00000267291.7	c.315A>C	p.Pro105Pro	synonymous_variant	Exon 1 of 2	1	NM_178861.5	ENSP00000267291.6
FARP1	ENST00000319562.11	c.-24+33430T>G		intron_variant	Intron 1 of 26	1	NM_005766.4	ENSP00000322926.6

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD3 exomes AF: 0.00000817 AC: 2 AN: 244700 Hom.: 0 AF XY: 0.0000151 AC XY: 2 AN XY: 132862

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 SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452238 Hom.: 0 Cov.: 88 AF XY: 0.00000138 AC XY: 1 AN XY: 722864

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.74
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs628778; hg19: chr13-98829176;