Variant 20-35953998-C-T 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_033630.3(SCAND1):c.287G>A(p.Gly96Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000843 in 1,549,832 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00086 ( 1 hom. )

Consequence

SCAND1
NM_033630.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42

Variant links:

Genes affected

SCAND1 (HGNC:10566): (SCAN domain containing 1) This gene encodes a SCAN box domain-containing protein. The SCAN domain is a highly conserved, leucine-rich motif of approximately 60 aa originally found within a subfamily of zinc finger proteins. This gene belongs to a family of genes that encode an isolated SCAN domain, but no zinc finger motif. This protein binds to and may regulate the function of the transcription factor myeloid zinc finger 1B. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jan 2011]

SCAND1 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=0.023825794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAND1	NM_033630.3 link	c.287G>A	p.Gly96Asp	missense_variant	2/2	ENST00000305978.7	NP_361012.3	P57086H0UIA5Q9NZG6
SCAND1	NM_001385710.1 link	c.287G>A	p.Gly96Asp	missense_variant	3/3		NP_001372639.1
SCAND1	NM_016558.4 link	c.287G>A	p.Gly96Asp	missense_variant	3/3		NP_057642.1	P57086Q9NZG6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SCAND1	ENST00000305978.7 link	c.287G>A	p.Gly96Asp	missense_variant	2/2	1	NM_033630.3	ENSP00000301995.2	P57086
SCAND1	ENST00000373991.3 link	c.287G>A	p.Gly96Asp	missense_variant	3/3	1		ENSP00000363103.3	P57086
SCAND1	ENST00000615116.1 link	c.287G>A	p.Gly96Asp	missense_variant	3/3	5		ENSP00000481289.1	P57086

Frequencies

GnomAD3 genomes

AF:

0.000663

AC:

101

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00126

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000532

AC:

AN:

148364

Hom.:

AF XY:

0.000474

AC XY:

AN XY:

80162

show subpopulations

Gnomad AFR exome

AF:

0.000277

Gnomad AMR exome

AF:

0.000161

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000869

Gnomad FIN exome

AF:

0.0000751

Gnomad NFE exome

AF:

0.00122

Gnomad OTH exome

AF:

0.000235

GnomAD4 exome

AF:

0.000863

AC:

1206

AN:

1397472

Hom.:

Cov.:

AF XY:

0.000831

AC XY:

573

AN XY:

689456

show subpopulations

Gnomad4 AFR exome

AF:

0.000253

Gnomad4 AMR exome

AF:

0.000167

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000138

Gnomad4 FIN exome

AF:

0.000303

Gnomad4 NFE exome

AF:

0.00105

Gnomad4 OTH exome

AF:

0.000518

GnomAD4 genome

AF:

0.000663

AC:

101

AN:

152360

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00126

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000985

Hom.:

Bravo

AF:

0.000657

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000243

AC:

ESP6500EA

AF:

0.000609

AC:

ExAC

AF:

0.000254

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Sep 15, 2021

The c.476G>A (p.G159D) alteration is located in exon 2 (coding exon 2) of the SCAND1 gene. This alteration results from a G to A substitution at nucleotide position 476, causing the glycine (G) at amino acid position 159 to be replaced by an aspartic acid (D). 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

0.14

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.019

T;T;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.41

.;T;.

M_CAP

Benign

0.0037

MetaRNN

Benign

0.024

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.90

L;L;L

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.78

N;.;N

REVEL

Benign

0.051

Sift

Benign

0.055

T;.;T

Sift4G

Benign

0.51

T;T;T

Polyphen

0.74

P;P;P

Vest4

0.29

MVP

0.27

MPC

1.4

ClinPred

0.026

GERP RS

1.4

Varity_R

0.063

gMVP

0.38

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