17-19414592-G-T

Position:

• chr17-19414592-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000461366.2(RNF112):​c.940G>T​(p.Asp314Tyr) 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 pathogenic outcome for this variant. 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: 2.39

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.887

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF112	NM_007148.5	c.940G>T	p.Asp314Tyr	missense_variant	9/14	ENST00000461366.2	NP_009079.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF112	ENST00000461366.2	c.940G>T	p.Asp314Tyr	missense_variant	9/14	1	NM_007148.5	ENSP00000454919	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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

Oct 06, 2021

The c.940G>T (p.D314Y) alteration is located in exon 9 (coding exon 9) of the RNF112 gene. This alteration results from a G to T substitution at nucleotide position 940, causing the aspartic acid (D) at amino acid position 314 to be replaced by a tyrosine (Y). 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	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.89	D
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.5	D
Sift	Benign	0.070	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.71
MVP		0.94
MPC		1.2
GERP RS		5.2
Varity_R		0.41
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: chr17-19317905;