chr15-76376199-C-T

Variant names:

Variant summary

Our verdict is The variant received 2 classification points (ACMG Germline Pathogenicity v2019). PM2

The NM_020843.4(SCAPER):c.3818G>A (p.Cys1273Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. The affected nucleotide is highly conserved across species (PhyloP 100-way vertebrate score: 7.51). Variant has been reported in ClinVar as Uncertain Significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SCAPER
NM_020843.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.51

Publications

0 publications found

Variant links:

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: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen
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

SCAPER links:

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new If you want to explore the variant's impact on the transcript NM_020843.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 points.

PM2

Absent from gnomAD (AD/XL gene) — PM2; Absent from gnomAD at well-covered site (MOI: AD+AR) (threshold 0.0001) — PM2 moderate.

Variant Effect in Transcripts

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

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCAPER	NM_020843.4	MANE Select	c.3818G>A	p.Cys1273Tyr	missense	Exon 29 of 32	NP_065894.2	Q9BY12-1
SCAPER	NM_001353009.2		c.3836G>A	p.Cys1279Tyr	missense	Exon 30 of 33	NP_001339938.1
SCAPER	NM_001353011.2		c.3434G>A	p.Cys1145Tyr	missense	Exon 30 of 33	NP_001339940.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCAPER	ENST00000563290.6	TSL:5 MANE Select	c.3818G>A	p.Cys1273Tyr	missense	Exon 29 of 32	ENSP00000454973.1	Q9BY12-1
SCAPER	ENST00000324767.11	TSL:1	c.3818G>A	p.Cys1273Tyr	missense	Exon 28 of 31	ENSP00000326924.7	Q9BY12-1
SCAPER	ENST00000538941.6	TSL:1	c.3080G>A	p.Cys1027Tyr	missense	Exon 29 of 32	ENSP00000442190.2	Q9BY12-3

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes					32
GnomAD4 exome					30
GnomAD4 genome					32

Showing 3 sources

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
AlphaGenome AVI	Pathogenic	-	32
AlphaMissense	Pathogenic	-	0.94
BayesDel_addAF	Pathogenic	D	0.25
BayesDel_noAF	Uncertain	-	0.12
CADD	Pathogenic	-	28
DANN	Uncertain	-	1.0
DEOGEN2	Benign	T	0.15
Eigen	Pathogenic	-	0.84
Eigen_PC	Pathogenic	-	0.84
FATHMM_MKL	Pathogenic	D	0.99
FuncVEP CTI	Pathogenic	-	0.90
GPN-Star LLR	N/A	-	-8.2
GPN-Star score	N/A	-	8.2
LIST_S2	Uncertain	D	0.96
M_CAP	Benign	D	0.047
MetaRNN	Pathogenic	D	0.81
MetaSVM	Benign	T	-0.91
MutationAssessor	Uncertain	M	2.7
PhyloP100	Uncertain	-	7.5
popEVE	Benign	-	-4.0
PrimateAI	Pathogenic	D	0.92
PROVEAN	Uncertain	D	-4.4
REVEL	Uncertain	-	0.45
Sift	Uncertain	D	0.013
Sift4G	Uncertain	D	0.014
Varity_R	N/A	-	0.60
VESM-3B	Benign	-	-12

Showing 27 of 27 scores

Splicing Scores

Algorithm	Calibrated prediction	Prediction	Score
Pangolin (max)	Benign	-	0.0
SpliceAI score (max)	Benign	- Details are displayed if max score is > 0.2	0.0

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

Publications

Other links and lift over