2-7024447-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_014746.6(RNF144A):c.588A>G(p.Glu196=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,612,408 control chromosomes in the GnomAD database, including 106,714 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7733 hom., cov: 33)
  • Exomes 𝑓: 0.36 (98981 hom.)
• Consequence: RNF144A NM_014746.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.325

Genes affected

RNF144A (HGNC:20457): (ring finger protein 144A) This gene encodes a member of a family of RING finger domain-containing E3 ubiquitin ligases that also includes parkin and parc. The expression of this gene is induced by DNA damage. The encoded protein interacts with the cytoplasmic DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) and promotes its degradation through ubiquitination. The orthologous mouse protein has been shown to interact with a ubiquitin-conjugating enzyme involved in embryonic development. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 2-7024447-A-G is Benign according to our data. Variant chr2-7024447-A-G is described in ClinVar as [Benign]. Clinvar id is 1250987.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.325 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF144A	NM_014746.6	c.588A>G	p.Glu196=	synonymous_variant	7/9	ENST00000320892.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF144A	ENST00000320892.11	c.588A>G	p.Glu196=	synonymous_variant	7/9	1	NM_014746.6	P1
RNF144A	ENST00000432850.1	c.576A>G	p.Glu192=	synonymous_variant	5/7	3
RNF144A	ENST00000467276.5	n.709A>G		non_coding_transcript_exon_variant	4/6	3

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45685 AN: 152074 Hom.: 7727 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.294

GnomAD3 exomes AF: 0.349 AC: 87710 AN: 251310 Hom.: 16237 AF XY: 0.355 AC XY: 48202 AN XY: 135846

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.401

Gnomad ASJ exome AF: 0.405

Gnomad EAS exome AF: 0.157

Gnomad SAS exome AF: 0.406

Gnomad FIN exome AF: 0.346

Gnomad NFE exome AF: 0.373

Gnomad OTH exome AF: 0.355

GnomAD4 exome AF: 0.364 AC: 531206 AN: 1460216 Hom.: 98981 Cov.: 40 AF XY: 0.366 AC XY: 265667 AN XY: 726056

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.402

Gnomad4 ASJ exome AF: 0.399

Gnomad4 EAS exome AF: 0.164

Gnomad4 SAS exome AF: 0.404

Gnomad4 FIN exome AF: 0.345

Gnomad4 NFE exome AF: 0.373

Gnomad4 OTH exome AF: 0.353

GnomAD4 genome AF: 0.300 AC: 45716 AN: 152192 Hom.: 7733 Cov.: 33 AF XY: 0.301 AC XY: 22380 AN XY: 74384

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.295

Alfa AF: 0.342 Hom.: 4824

Bravo AF: 0.296

Asia WGS AF: 0.262 AC: 909 AN: 3478

EpiCase AF: 0.364

EpiControl AF: 0.368

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 30, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	0.81
Dann	Benign	0.34

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

LitVar

Other links and lift over

dbSNP: rs376219; hg19: chr2-7164578; COSMIC: COSV57981222; COSMIC: COSV57981222;