17-19412524-A-G

Position:

• chr17-19412524-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000461366.2(RNF112):​c.122A>G​(p.Glu41Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,184 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: RNF112 ENST00000461366.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.848

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33676434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF112	NM_007148.5	c.122A>G	p.Glu41Gly	missense_variant	3/14	ENST00000461366.2	NP_009079.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF112	ENST00000461366.2	c.122A>G	p.Glu41Gly	missense_variant	3/14	1	NM_007148.5	ENSP00000454919	P1
	ENST00000579897.1	n.549+46T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461184 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 726870

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000989

Gnomad4 OTH exome AF: 0.00

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

Mar 03, 2022

The c.122A>G (p.E41G) alteration is located in exon 3 (coding exon 3) of the RNF112 gene. This alteration results from a A to G substitution at nucleotide position 122, causing the glutamic acid (E) at amino acid position 41 to be replaced by a glycine (G). 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	0.15
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.17	.;T
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.76	T;T
M_CAP	Pathogenic	0.52	D
MetaRNN	Benign	0.34	T;T
MutationAssessor	Benign	1.1	.;L
MutationTaster	Benign	1.0	D;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.97	.;N
Sift	Pathogenic	0.0	.;D
Sift4G	Benign	0.16	T;D
Polyphen		1.0	.;D
Vest4		0.36
MVP		0.85
MPC		0.98
GERP RS		4.8
Varity_R		0.17
gMVP		0.46

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: chr17-19315837;