8-143791252-C-G

Variant names:

• chr8-143791252-C-G
• rs782521316
• NM_182706.5:c.4879G>C

Variant summary

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

The NM_182706.5(SCRIB):​c.4879G>C​(p.Gly1627Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000739 in 1,353,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. G1627V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: SCRIB NM_182706.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 0 publications found

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]

SCRIB Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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=0.1560202).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182706.5. 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
	SCRIB	NM_182706.5	MANE Select	c.4879G>C	p.Gly1627Arg	missense	Exon 37 of 37	NP_874365.3
	SCRIB	NM_015356.5		c.4804G>C	p.Gly1602Arg	missense	Exon 36 of 36	NP_056171.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCRIB	ENST00000356994.7	TSL:2 MANE Select	c.4879G>C	p.Gly1627Arg	missense	Exon 37 of 37	ENSP00000349486.2	Q14160-3
	SCRIB	ENST00000320476.7	TSL:1	c.4804G>C	p.Gly1602Arg	missense	Exon 36 of 36	ENSP00000322938.3	Q14160-1
	SCRIB	ENST00000377533.7	TSL:1	c.4561G>C	p.Gly1521Arg	missense	Exon 36 of 36	ENSP00000366756.3	Q14160-2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000755 AC: 1 AN: 132398 AF XY: 0.0000143

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.39e-7 AC: 1 AN: 1353374 Hom.: 0 Cov.: 31 AF XY: 0.00000151 AC XY: 1 AN XY: 663332

African (AFR) AF: 0.00 AC: 0 AN: 29870

American (AMR) AF: 0.00 AC: 0 AN: 27762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20808

East Asian (EAS) AF: 0.00 AC: 0 AN: 36594

South Asian (SAS) AF: 0.00 AC: 0 AN: 70964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5424

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1059134

Other (OTH) AF: 0.0000179 AC: 1 AN: 55740

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000844 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.0
DANN	Uncertain	0.99
DEOGEN2	Benign	0.074	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.091	N
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.3
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.013	D
Vest4		0.14
MutPred		0.077		Gain of solvent accessibility (P = 0.019)
MVP		0.25
ClinPred		0.42	T
GERP RS		-0.0015
gMVP		0.041
Mutation Taster		=97/3	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: rs782521316; hg19: chr8-144873422;