rs651627

Variant names:

• chr12-120571395-C-T
• rs651627
• NM_014868.5:c.2142+104C>T

Variant summary

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

The NM_014868.5(RNF10):​c.2142+104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 836,396 control chromosomes in the GnomAD database, including 41,292 homozygotes. 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: 𝑓 0.26 (5975 hom., cov: 31)
  • Exomes 𝑓: 0.31 (35317 hom.)
• Consequence: RNF10 NM_014868.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727
• Publications: 15 publications found

Genes affected

RNF10 (HGNC:10055): (ring finger protein 10) The protein encoded by this gene contains a ring finger motif, which is known to be involved in protein-protein interactions. The specific function of this protein has not yet been determined. EST data suggests the existence of multiple alternatively spliced transcript variants, however, their full length nature is not known. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014868.5. 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
	RNF10	NM_014868.5	MANE Select	c.2142+104C>T		intron	N/A	NP_055683.3
	RNF10	NM_001330474.2		c.2157+104C>T		intron	N/A	NP_001317403.1	Q8N5U6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF10	ENST00000325954.9	TSL:1 MANE Select	c.2142+104C>T		intron	N/A	ENSP00000322242.4	Q8N5U6-1
	RNF10	ENST00000413266.6	TSL:5	c.2157+104C>T		intron	N/A	ENSP00000415682.2	Q8N5U6-2
	RNF10	ENST00000538254.1	TSL:3	c.147+104C>T		intron	N/A	ENSP00000441487.1	H0YG28

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39595 AN: 151924 Hom.: 5962 Cov.: 31

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.315 AC: 215426 AN: 684354 Hom.: 35317 AF XY: 0.315 AC XY: 113489 AN XY: 359872

African (AFR) AF: 0.111 AC: 2027 AN: 18202

American (AMR) AF: 0.308 AC: 10217 AN: 33218

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 4236 AN: 17926

East Asian (EAS) AF: 0.509 AC: 17825 AN: 35022

South Asian (SAS) AF: 0.304 AC: 18629 AN: 61358

European-Finnish (FIN) AF: 0.327 AC: 13329 AN: 40770

Middle Eastern (MID) AF: 0.255 AC: 931 AN: 3650

European-Non Finnish (NFE) AF: 0.314 AC: 137981 AN: 439858

Other (OTH) AF: 0.298 AC: 10251 AN: 34350

GnomAD4 genome AF: 0.261 AC: 39620 AN: 152042 Hom.: 5975 Cov.: 31 AF XY: 0.264 AC XY: 19646 AN XY: 74298

African (AFR) AF: 0.115 AC: 4765 AN: 41490

American (AMR) AF: 0.275 AC: 4190 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 808 AN: 3472

East Asian (EAS) AF: 0.503 AC: 2601 AN: 5166

South Asian (SAS) AF: 0.300 AC: 1448 AN: 4830

European-Finnish (FIN) AF: 0.331 AC: 3486 AN: 10532

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21515 AN: 67978

Other (OTH) AF: 0.247 AC: 521 AN: 2108

Alfa AF: 0.285 Hom.: 1662

Bravo AF: 0.251

Asia WGS AF: 0.354 AC: 1233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.80
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

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: rs651627; hg19: chr12-121009198; COSMIC: COSV58045399; COSMIC: COSV58045399;