NM_020843.4:c.4200A>C

Variant names:

• chr15-76348636-T-G
• rs918249904
• NM_020843.4:c.4200A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020843.4(SCAPER):​c.4200A>C​(p.Lys1400Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000261 in 1,533,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: SCAPER NM_020843.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01
• Publications: 0 publications found

Genes affected

SCAPER (HGNC:13081): (S-phase cyclin A associated protein in the ER) Predicted to enable nucleic acid binding activity and zinc ion binding activity. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

SCAPER Gene-Disease associations (from GenCC):

• intellectual developmental disorder and retinitis pigmentosa; IDDRP

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• neurodevelopmental disorder

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16442776).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020843.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAPER	NM_020843.4	MANE Select	c.4200A>C	p.Lys1400Asn	missense	Exon 32 of 32	NP_065894.2	Q9BY12-1
	SCAPER	NM_001353009.2		c.4218A>C	p.Lys1406Asn	missense	Exon 33 of 33	NP_001339938.1
	SCAPER	NM_001353011.2		c.3816A>C	p.Lys1272Asn	missense	Exon 33 of 33	NP_001339940.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAPER	ENST00000563290.6	TSL:5 MANE Select	c.4200A>C	p.Lys1400Asn	missense	Exon 32 of 32	ENSP00000454973.1	Q9BY12-1
	SCAPER	ENST00000324767.11	TSL:1	c.4200A>C	p.Lys1400Asn	missense	Exon 31 of 31	ENSP00000326924.7	Q9BY12-1
	SCAPER	ENST00000538941.6	TSL:1	c.3462A>C	p.Lys1154Asn	missense	Exon 32 of 32	ENSP00000442190.2	Q9BY12-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000217 AC: 3 AN: 1381456 Hom.: 0 Cov.: 28 AF XY: 0.00000294 AC XY: 2 AN XY: 681388

African (AFR) AF: 0.00 AC: 0 AN: 30686

American (AMR) AF: 0.00 AC: 0 AN: 31902

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24640

East Asian (EAS) AF: 0.00 AC: 0 AN: 35756

South Asian (SAS) AF: 0.00 AC: 0 AN: 75670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5636

European-Non Finnish (NFE) AF: 0.00000280 AC: 3 AN: 1070260

Other (OTH) AF: 0.00 AC: 0 AN: 57446

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74376

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0075	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.0
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.071
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.10
MVP		0.52
MPC		1.0
ClinPred		0.95	D
GERP RS		4.5
Varity_R		0.39
gMVP		0.37
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs918249904; hg19: chr15-76640977;