chr8-143791908-C-G

Variant names:

• chr8-143791908-C-G
• rs117338714
• NM_182706.5:c.4663G>C

Variant summary

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

The NM_182706.5(SCRIB):​c.4663G>C​(p.Gly1555Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000738 in 1,354,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1555S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: SCRIB NM_182706.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677

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=0.115329295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCRIB	NM_182706.5	c.4663G>C	p.Gly1555Arg	missense_variant	Exon 34 of 37	ENST00000356994.7	NP_874365.3
SCRIB	NM_015356.5	c.4663G>C	p.Gly1555Arg	missense_variant	Exon 34 of 36		NP_056171.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCRIB	ENST00000356994.7	c.4663G>C	p.Gly1555Arg	missense_variant	Exon 34 of 37	2	NM_182706.5	ENSP00000349486.2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 7.38e-7 AC: 1 AN: 1354882 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 662650

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: 9.44e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.072	.;T;T
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.037	N
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.97	T
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.73	N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.012	D;T;D
Vest4		0.29
MutPred		0.12		Gain of solvent accessibility (P = 0.0674);Gain of solvent accessibility (P = 0.0674);.;
MVP		0.23
ClinPred		0.51	D
GERP RS		-2.1
gMVP		0.097

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: rs117338714; hg19: chr8-144874078;