chr17-19414654-C-G

Variant names:

• chr17-19414654-C-G
• NM_007148.5:c.1002C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007148.5(RNF112):​c.1002C>G​(p.Ile334Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF112 NM_007148.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0790
• Publications: 0 publications found

Genes affected

RNF112 (HGNC:12968): (ring finger protein 112) This gene encodes a member of the RING finger protein family of transcription factors. The protein is primarily expressed in brain. The gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08328545).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007148.5. 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
	RNF112	NM_007148.5	MANE Select	c.1002C>G	p.Ile334Met	missense	Exon 9 of 14	NP_009079.2	Q9ULX5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF112	ENST00000461366.2	TSL:1 MANE Select	c.1002C>G	p.Ile334Met	missense	Exon 9 of 14	ENSP00000454919.1	Q9ULX5-1
	RNF112	ENST00000908744.1		c.1002C>G	p.Ile334Met	missense	Exon 10 of 15	ENSP00000578803.1
	RNF112	ENST00000908743.1		c.831C>G	p.Ile277Met	missense	Exon 10 of 15	ENSP00000578802.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.6
DANN	Benign	0.68
DEOGEN2	Benign	0.15	T
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.083	T
MutationAssessor	Benign	0.64	N
PhyloP100		-0.079
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.77	N
Sift	Benign	0.091	T
Sift4G	Benign	0.16	T
Polyphen		0.026	B
Vest4		0.22
MVP		0.84
MPC		0.41
GERP RS		0.046
Varity_R		0.074
gMVP		0.22

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

hg19: chr17-19317967;