17-19414128-G-A

Position:

• chr17-19414128-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000461366.2(RNF112):​c.859G>A​(p.Asp287Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF112 ENST00000461366.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.36

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF112	NM_007148.5	c.859G>A	p.Asp287Asn	missense_variant	7/14	ENST00000461366.2	NP_009079.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF112	ENST00000461366.2	c.859G>A	p.Asp287Asn	missense_variant	7/14	1	NM_007148.5	ENSP00000454919	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2023

The c.859G>A (p.D287N) alteration is located in exon 7 (coding exon 7) of the RNF112 gene. This alteration results from a G to A substitution at nucleotide position 859, causing the aspartic acid (D) at amino acid position 287 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.68	D
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.28	D
MetaRNN	Uncertain	0.70	D
MutationAssessor	Pathogenic	3.0	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.5	D
Sift	Uncertain	0.0090	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.48
MVP		0.91
MPC		1.0
GERP RS		4.9
Varity_R		0.39
gMVP		0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-19317441;