Variant 20-35954046-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.239C>T(p.Pro80Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000435 in 1,541,394 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 0.00050 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00043 ( 1 hom. )

Consequence

SCAND1
NM_033630.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.00

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=0.031639785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SCAND1	NM_033630.3 linkuse as main transcript	c.239C>T	p.Pro80Leu	missense_variant	2/2	ENST00000305978.7
SCAND1	NM_001385710.1 linkuse as main transcript	c.239C>T	p.Pro80Leu	missense_variant	3/3
SCAND1	NM_016558.4 linkuse as main transcript	c.239C>T	p.Pro80Leu	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SCAND1	ENST00000305978.7 linkuse as main transcript	c.239C>T	p.Pro80Leu	missense_variant	2/2	1	NM_033630.3	P1
SCAND1	ENST00000373991.3 linkuse as main transcript	c.239C>T	p.Pro80Leu	missense_variant	3/3	1		P1
SCAND1	ENST00000615116.1 linkuse as main transcript	c.239C>T	p.Pro80Leu	missense_variant	3/3	5		P1

Frequencies

GnomAD3 genomes

AF:

0.000499

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000911

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000460

AC:

AN:

141346

Hom.:

AF XY:

0.000406

AC XY:

AN XY:

76372

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000165

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00150

Gnomad NFE exome

AF:

0.000804

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000428

AC:

595

AN:

1389164

Hom.:

Cov.:

AF XY:

0.000462

AC XY:

316

AN XY:

684010

show subpopulations

Gnomad4 AFR exome

AF:

0.0000318

Gnomad4 AMR exome

AF:

0.000170

Gnomad4 ASJ exome

AF:

0.0000400

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00128

Gnomad4 NFE exome

AF:

0.000478

Gnomad4 OTH exome

AF:

0.000278

GnomAD4 genome

AF:

0.000499

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.000911

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000714

Hom.:

Bravo

AF:

0.000340

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

Jun 11, 2021

The c.428C>T (p.P143L) 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 428, causing the proline (P) at amino acid position 143 to be replaced by a leucine (L). 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

0.083

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.018

T;T;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.48

.;T;.

M_CAP

Benign

0.028

MetaRNN

Benign

0.032

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.55

N;N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.65

N;.;N

REVEL

Benign

0.084

Sift

Benign

0.23

T;.;T

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

0.93

P;P;P

Vest4

0.055

MVP

0.44

MPC

0.81

ClinPred

0.093

GERP RS

4.8

Varity_R

0.070

gMVP

0.36

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