Variant 20-35954241-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_033630.3(SCAND1):c.44C>T(p.Ala15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,650 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SCAND1
NM_033630.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.756

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:

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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=0.067070246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAND1	NM_033630.3 linkuse as main transcript	c.44C>T	p.Ala15Val	missense_variant	2/2	ENST00000305978.7	NP_361012.3	P57086H0UIA5Q9NZG6
SCAND1	NM_001385710.1 linkuse as main transcript	c.44C>T	p.Ala15Val	missense_variant	3/3		NP_001372639.1
SCAND1	NM_016558.4 linkuse as main transcript	c.44C>T	p.Ala15Val	missense_variant	3/3		NP_057642.1	P57086Q9NZG6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SCAND1	ENST00000305978.7 linkuse as main transcript	c.44C>T	p.Ala15Val	missense_variant	2/2	1	NM_033630.3	ENSP00000301995.2	P57086
SCAND1	ENST00000373991.3 linkuse as main transcript	c.44C>T	p.Ala15Val	missense_variant	3/3	1		ENSP00000363103.3	P57086
SCAND1	ENST00000615116.1 linkuse as main transcript	c.44C>T	p.Ala15Val	missense_variant	3/3	5		ENSP00000481289.1	P57086

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245752

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134378

show subpopulations

Gnomad AFR exome

AF:

0.0000671

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:

0.00000205

AC:

AN:

1460650

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726700

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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 10, 2023

The c.233C>T (p.A78V) alteration is located in exon 2 (coding exon 2) of the SCAND1 gene. This alteration results from a C to T substitution at nucleotide position 233, causing the alanine (A) at amino acid position 78 to be replaced by a valine (V). 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

0.088

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

T;T;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.54

.;T;.

M_CAP

Benign

0.0028

MetaRNN

Benign

0.067

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.0

L;L;L

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.59

N;.;N

REVEL

Benign

0.044

Sift

Benign

0.046

D;.;D

Sift4G

Benign

0.11

T;T;T

Polyphen

0.072

B;B;B

Vest4

0.12

MutPred

0.076

Loss of glycosylation at P18 (P = 0.1931);Loss of glycosylation at P18 (P = 0.1931);Loss of glycosylation at P18 (P = 0.1931);

MVP

0.20

MPC

0.85

ClinPred

0.095

GERP RS

2.9

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.1

Varity_R

0.072

gMVP

0.22

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