chr8-143791237-C-T

Variant names:

• chr8-143791237-C-T
• rs201742088
• NM_182706.5:c.4894G>A

Variant summary

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

The NM_182706.5(SCRIB):​c.4894G>A​(p.Glu1632Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000299 in 1,336,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: SCRIB NM_182706.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

Genes affected

SCRIB (HGNC:30377): (scribble planar cell polarity protein) This gene encodes a protein that was identified as being similar to the Drosophila scribble protein. The mammalian protein is involved in tumor suppression pathways. As a scaffold protein involved in cell polarization processes, this protein binds to many other proteins. The encoded protein binds to papillomavirus E6 protein via its PDZ domain and the C-terminus of E6. Two alternatively spliced transcript variants that encode different protein isoforms have been found for this gene. [provided by RefSeq, Nov 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=0.24075794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCRIB	NM_182706.5	c.4894G>A	p.Glu1632Lys	missense_variant	Exon 37 of 37	ENST00000356994.7	NP_874365.3
SCRIB	NM_015356.5	c.4819G>A	p.Glu1607Lys	missense_variant	Exon 36 of 36		NP_056171.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCRIB	ENST00000356994.7	c.4894G>A	p.Glu1632Lys	missense_variant	Exon 37 of 37	2	NM_182706.5	ENSP00000349486.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000299 AC: 4 AN: 1336220 Hom.: 0 Cov.: 31 AF XY: 0.00000460 AC XY: 3 AN XY: 652728

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: 0.00000381

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.096	.;T;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.39	T
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.16
MutPred		0.23		.;Gain of MoRF binding (P = 0.0073);.;
MVP		0.49
ClinPred		0.78	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.099

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: rs201742088; hg19: chr8-144873407;