Variant chr19-10092270-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018381.4(SHFL):c.844G>A(p.Val282Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 1,599,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SHFL
NM_018381.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.16

Variant links:

Genes affected

SHFL (HGNC:25649): (shiftless antiviral inhibitor of ribosomal frameshifting) This gene is an interferon stimulated gene (ISG) that inhibits viral replication. The encoded protein binds nucleic acids and inhibits programmed -1 ribosomal frameshifting required for translation by many RNA viruses. Viruses inhibited by the protein include Zika virus, dengue virus and the coronaviruses, SARS-CoV and SARS-CoV2. [provided by RefSeq, Aug 2021]

SHFL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03633365).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SHFL	NM_018381.4 linkuse as main transcript	c.844G>A	p.Val282Met	missense_variant	8/8	ENST00000253110.16
SHFL	NM_001308277.2 linkuse as main transcript	c.736G>A	p.Val246Met	missense_variant	8/8
SHFL	XM_047439046.1 linkuse as main transcript	c.727G>A	p.Val243Met	missense_variant	7/7
SHFL	XM_047439047.1 linkuse as main transcript	c.691G>A	p.Val231Met	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHFL	ENST00000253110.16 linkuse as main transcript	c.844G>A	p.Val282Met	missense_variant	8/8	2	NM_018381.4	P1	Q9NUL5-1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.0000273

AC:

AN:

219812

Hom.:

AF XY:

0.0000335

AC XY:

AN XY:

119292

show subpopulations

Gnomad AFR exome

AF:

0.000461

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1447616

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

719130

show subpopulations

Gnomad4 AFR exome

AF:

0.000363

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.05e-7

Gnomad4 OTH exome

AF:

0.0000334

GnomAD4 genome

AF:

0.000171

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.000482

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000129

Hom.:

Bravo

AF:

0.000189

ESP6500AA

AF:

0.000482

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000498

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.844G>A (p.V282M) alteration is located in exon 8 (coding exon 8) of the C19orf66 gene. This alteration results from a G to A substitution at nucleotide position 844, causing the valine (V) at amino acid position 282 to be replaced by a methionine (M). 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

0.12

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.67

T;T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.036

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

-0.18

N;.;N

REVEL

Benign

0.11

Sift

Benign

0.057

T;.;T

Sift4G

Pathogenic

0.0

D;D;D

Vest4

0.071

MVP

0.23

MPC

1.5

ClinPred

0.12

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.28

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over