8-143791171-G-A

Variant names:

• chr8-143791171-G-A
• rs1554632473
• NM_182706.5:c.4960C>T

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.4960C>T​(p.Pro1654Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCRIB NM_182706.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.04
• 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=0.23799565).

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.4960C>T	p.Pro1654Ser	missense	Exon 37 of 37	NP_874365.3
	SCRIB	NM_015356.5		c.4885C>T	p.Pro1629Ser	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.4960C>T	p.Pro1654Ser	missense	Exon 37 of 37	ENSP00000349486.2	Q14160-3
	SCRIB	ENST00000320476.7	TSL:1	c.4885C>T	p.Pro1629Ser	missense	Exon 36 of 36	ENSP00000322938.3	Q14160-1
	SCRIB	ENST00000377533.7	TSL:1	c.4642C>T	p.Pro1548Ser	missense	Exon 36 of 36	ENSP00000366756.3	Q14160-2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000147 AC: 1 AN: 67942 AF XY: 0.0000298

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000113

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.83e-7 AC: 1 AN: 1277422 Hom.: 0 Cov.: 31 AF XY: 0.00000162 AC XY: 1 AN XY: 616270

African (AFR) AF: 0.00 AC: 0 AN: 27428

American (AMR) AF: 0.0000561 AC: 1 AN: 17840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18512

East Asian (EAS) AF: 0.00 AC: 0 AN: 33162

South Asian (SAS) AF: 0.00 AC: 0 AN: 56768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4620

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1022308

Other (OTH) AF: 0.00 AC: 0 AN: 52678

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	0.00069	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.66	D
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.51	T
PhyloP100		3.0
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.30
MutPred		0.20		Gain of phosphorylation at P1629 (P = 0.0081)
MVP		0.40
ClinPred		0.60	D
GERP RS		4.2
gMVP		0.043
Mutation Taster		=79/21	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: rs1554632473; hg19: chr8-144873341;