20-35954089-C-G

Position:

• chr20-35954089-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033630.3(SCAND1):​c.196G>C​(p.Ala66Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,384,778 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: 0.000011 (0 hom.)
• Consequence: SCAND1 NM_033630.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.585

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09547594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAND1	NM_033630.3	c.196G>C	p.Ala66Pro	missense_variant	2/2	ENST00000305978.7	NP_361012.3
SCAND1	NM_001385710.1	c.196G>C	p.Ala66Pro	missense_variant	3/3		NP_001372639.1
SCAND1	NM_016558.4	c.196G>C	p.Ala66Pro	missense_variant	3/3		NP_057642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAND1	ENST00000305978.7	c.196G>C	p.Ala66Pro	missense_variant	2/2	1	NM_033630.3	ENSP00000301995.2
SCAND1	ENST00000373991.3	c.196G>C	p.Ala66Pro	missense_variant	3/3	1		ENSP00000363103.3
SCAND1	ENST00000615116.1	c.196G>C	p.Ala66Pro	missense_variant	3/3	5		ENSP00000481289.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000108 AC: 15 AN: 1384778 Hom.: 0 Cov.: 33 AF XY: 0.00000881 AC XY: 6 AN XY: 680662

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: 0.0000140

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

Apr 06, 2022

The c.385G>C (p.A129P) alteration is located in exon 2 (coding exon 2) of the SCAND1 gene. This alteration results from a G to C substitution at nucleotide position 385, causing the alanine (A) at amino acid position 129 to be replaced by a proline (P). 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	0.080
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.013	T;T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.52	.;T;.
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.095	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;L;L
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.24	N;.;N
REVEL	Benign	0.072
Sift	Benign	0.20	T;.;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.0030	B;B;B
Vest4		0.30
MutPred		0.24		Gain of loop (P = 0.0013);Gain of loop (P = 0.0013);Gain of loop (P = 0.0013);
MVP		0.32
MPC		1.4
ClinPred		0.21	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.29

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: chr20-34542011;