Genetic Variant NM_006913.4:c.46C>T (chr6-32178557-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate

The NM_006913.4(RNF5):c.46C>T(p.Arg16Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,457,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

RNF5
NM_006913.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.357

Publications

0 publications found

Variant links:

Genes affected

RNF5 (HGNC:10068): (ring finger protein 5) The protein encoded by this gene contains a RING finger, which is a motif known to be involved in protein-protein interactions. This protein is a membrane-bound ubiquitin ligase. It can regulate cell motility by targeting paxillin ubiquitination and altering the distribution and localization of paxillin in cytoplasm and cell focal adhesions. [provided by RefSeq, Jul 2008]

RNF5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34643674).

BP6

Variant 6-32178557-C-T is Benign according to our data. Variant chr6-32178557-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2273728.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006913.4. 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
	RNF5	NM_006913.4	MANE Select	c.46C>T	p.Arg16Cys	missense	Exon 1 of 6	NP_008844.1	Q99942

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF5	ENST00000375094.4	TSL:1 MANE Select	c.46C>T	p.Arg16Cys	missense	Exon 1 of 6	ENSP00000364235.3	Q99942
RNF5	ENST00000876421.1		c.46C>T	p.Arg16Cys	missense	Exon 1 of 6	ENSP00000546480.1
RNF5	ENST00000876424.1		c.46C>T	p.Arg16Cys	missense	Exon 1 of 6	ENSP00000546483.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000831

AC:

AN:

240592

AF XY:

0.0000151

show subpopulations

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:

0.0000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1457234

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

725032

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33424

American (AMR)

AF:

0.00

AC:

AN:

44554

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26056

East Asian (EAS)

AF:

0.00

AC:

AN:

39640

South Asian (SAS)

AF:

0.00

AC:

AN:

86080

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50814

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000180

AC:

AN:

1110628

Other (OTH)

AF:

0.00

AC:

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000856

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.76

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.35

MetaSVM

Uncertain

0.68

MutationAssessor

Benign

1.1

PhyloP100

0.36

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.60

Sift

Uncertain

0.018

Sift4G

Uncertain

0.035

Polyphen

1.0

Vest4

0.18

MutPred

0.22

Loss of loop (P = 0.0603)

MVP

0.93

MPC

0.88

ClinPred

0.84

GERP RS

4.3

PromoterAI

-0.074

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

gMVP

0.47

Mutation Taster

=75/25

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over