20-35953782-C-T

Position:

• chr20-35953782-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033630.3(SCAND1):​c.503G>A​(p.Arg168Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCAND1 NM_033630.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31112605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAND1	NM_033630.3	c.503G>A	p.Arg168Gln	missense_variant	2/2	ENST00000305978.7	NP_361012.3
SCAND1	NM_001385710.1	c.503G>A	p.Arg168Gln	missense_variant	3/3		NP_001372639.1
SCAND1	NM_016558.4	c.503G>A	p.Arg168Gln	missense_variant	3/3		NP_057642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAND1	ENST00000305978.7	c.503G>A	p.Arg168Gln	missense_variant	2/2	1	NM_033630.3	ENSP00000301995.2
SCAND1	ENST00000373991.3	c.503G>A	p.Arg168Gln	missense_variant	3/3	1		ENSP00000363103.3
SCAND1	ENST00000615116.1	c.503G>A	p.Arg168Gln	missense_variant	3/3	5		ENSP00000481289.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1346858 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 660528

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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.: 33

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

May 13, 2024

The c.692G>A (p.R231Q) 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 692, causing the arginine (R) at amino acid position 231 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	0.25
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.064	T;T;T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.75	.;T;.
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;L;L
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.080	N;.;N
REVEL	Benign	0.17
Sift	Uncertain	0.0040	D;.;D
Sift4G	Benign	0.10	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.29
MutPred		0.62		Loss of methylation at R168 (P = 0.0429);Loss of methylation at R168 (P = 0.0429);Loss of methylation at R168 (P = 0.0429);
MVP		0.31
MPC		2.0
ClinPred		0.75	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-34541704;