Genetic Variant SKIDA1:p.Arg789Gln (chr10-21515457-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_207371.4(SKIDA1):c.2366G>A(p.Arg789Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000864 in 1,613,998 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00089 ( 2 hom. )

Consequence

SKIDA1
NM_207371.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.65

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.038672626).

BS2

High AC in GnomAd4 at 91 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKIDA1	NM_207371.4 link	c.2366G>A	p.Arg789Gln	missense_variant	Exon 4 of 4	ENST00000449193.7	NP_997254.3	Q1XH10-1
SKIDA1	XM_047425204.1 link	c.2366G>A	p.Arg789Gln	missense_variant	Exon 2 of 2		XP_047281160.1
SKIDA1	XM_047425205.1 link	c.2366G>A	p.Arg789Gln	missense_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.2366G>A	p.Arg789Gln	missense_variant	Exon 4 of 4	3	NM_207371.4	ENSP00000410041.2		Q1XH10-1
SKIDA1	ENST00000444772.3 link	c.2129G>A	p.Arg710Gln	missense_variant	Exon 2 of 2	5		ENSP00000442432.1		Q1XH10-2

Frequencies

GnomAD3 genomes

AF:

0.000598

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000598

AC:

149

AN:

249190

Hom.:

AF XY:

0.000614

AC XY:

AN XY:

135186

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.000696

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000850

Gnomad FIN exome

AF:

0.0000929

Gnomad NFE exome

AF:

0.000894

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.000891

AC:

1303

AN:

1461688

Hom.:

Cov.:

AF XY:

0.000908

AC XY:

660

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.000804

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000823

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000998

Gnomad4 OTH exome

AF:

0.00116

GnomAD4 genome

AF:

0.000597

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00109

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000807

Hom.:

Bravo

AF:

0.000627

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000856

AC:

ExAC

AF:

0.000654

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000981

EpiControl

AF:

0.00101

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2366G>A (p.R789Q) alteration is located in exon 4 (coding exon 1) of the SKIDA1 gene. This alteration results from a G to A substitution at nucleotide position 2366, causing the arginine (R) at amino acid position 789 to be replaced by a glutamine (Q). 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

0.19

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Pathogenic

1.0

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-0.68

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.27

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.0050

D;D

Vest4

0.34

MVP

0.20

ClinPred

0.094

GERP RS

5.8

Varity_R

0.28

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