Genetic Variant SKIDA1:p.Glu814Glu (chr10-21515381-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_207371.4(SKIDA1):c.2442G>A(p.Glu814Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,613,974 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

SKIDA1
NM_207371.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.77

Variant links:

Genes affected

SKIDA1 (HGNC:32697): (SKI/DACH domain containing 1)

SKIDA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 10-21515381-C-T is Benign according to our data. Variant chr10-21515381-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3058032.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.77 with no splicing effect.

BS2

High AC in GnomAd4 at 45 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKIDA1	NM_207371.4 link	c.2442G>A	p.Glu814Glu	synonymous_variant	Exon 4 of 4	ENST00000449193.7	NP_997254.3	Q1XH10-1
SKIDA1	XM_047425204.1 link	c.2442G>A	p.Glu814Glu	synonymous_variant	Exon 2 of 2		XP_047281160.1
SKIDA1	XM_047425205.1 link	c.2442G>A	p.Glu814Glu	synonymous_variant	Exon 2 of 2		XP_047281161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKIDA1	ENST00000449193.7 link	c.2442G>A	p.Glu814Glu	synonymous_variant	Exon 4 of 4	3	NM_207371.4	ENSP00000410041.2		Q1XH10-1
SKIDA1	ENST00000444772.3 link	c.2205G>A	p.Glu735Glu	synonymous_variant	Exon 2 of 2	5		ENSP00000442432.1		Q1XH10-2

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000144

AC:

AN:

249266

Hom.:

AF XY:

0.000148

AC XY:

AN XY:

135228

show subpopulations

Gnomad AFR exome

AF:

0.00103

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000127

AC:

185

AN:

1461710

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000836

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000296

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000984

Hom.:

Bravo

AF:

0.000370

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SKIDA1-related disorder

Benign:1

Feb 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

8.5

DANN

Benign

0.54

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