20-35954196-G-A

Position:

• chr20-35954196-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033630.3(SCAND1):​c.89C>T​(p.Ala30Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,459,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000055 (0 hom.)
• Consequence: SCAND1 NM_033630.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.360

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]

ACMG classification

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=0.036867917).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAND1	NM_033630.3	c.89C>T	p.Ala30Val	missense_variant	2/2	ENST00000305978.7	NP_361012.3
SCAND1	NM_001385710.1	c.89C>T	p.Ala30Val	missense_variant	3/3		NP_001372639.1
SCAND1	NM_016558.4	c.89C>T	p.Ala30Val	missense_variant	3/3		NP_057642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAND1	ENST00000305978.7	c.89C>T	p.Ala30Val	missense_variant	2/2	1	NM_033630.3	ENSP00000301995.2
SCAND1	ENST00000373991.3	c.89C>T	p.Ala30Val	missense_variant	3/3	1		ENSP00000363103.3
SCAND1	ENST00000615116.1	c.89C>T	p.Ala30Val	missense_variant	3/3	5		ENSP00000481289.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1459702 Hom.: 0 Cov.: 33 AF XY: 0.00000826 AC XY: 6 AN XY: 726256

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2024

The c.278C>T (p.A93V) 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 278, causing the alanine (A) at amino acid position 93 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	0.074
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.94
DEOGEN2	Benign	0.013	T;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.29	.;T;.
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.037	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.40	N;.;N
REVEL	Benign	0.035
Sift	Benign	0.12	T;.;T
Sift4G	Benign	0.091	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.029
MutPred		0.11		Loss of glycosylation at S29 (P = 0.1016);Loss of glycosylation at S29 (P = 0.1016);Loss of glycosylation at S29 (P = 0.1016);
MVP		0.21
MPC		0.79
ClinPred		0.086	T
GERP RS		-9.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.034
gMVP		0.12

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

Other links and lift over

dbSNP: rs2056216153; hg19: chr20-34542118;