Genetic Variant SCRT2:p.Ala138Pro (chr20-664183-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033129.4(SCRT2):c.412G>C(p.Ala138Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000109 in 914,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A138G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000011 ( 0 hom. )

Consequence

SCRT2
NM_033129.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.501

Publications

0 publications found

Variant links:

Genes affected

SCRT2 (HGNC:15952): (scratch family transcriptional repressor 2) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in negative regulation of extrinsic apoptotic signaling pathway via death domain receptors and negative regulation of transcription by RNA polymerase II. Predicted to act upstream of or within regulation of neuron migration. Predicted to be located in chromatin. [provided by Alliance of Genome Resources, Apr 2022]

SCRT2 links:

ENSG00000270299 (HGNC:):

ENSG00000270299 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.065972745).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033129.4. 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
	SCRT2	NM_033129.4	MANE Select	c.412G>C	p.Ala138Pro	missense	Exon 2 of 2	NP_149120.1	Q9NQ03

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCRT2	ENST00000246104.7	TSL:1 MANE Select	c.412G>C	p.Ala138Pro	missense	Exon 2 of 2	ENSP00000246104.5	Q9NQ03
ENSG00000270299	ENST00000488788.2	TSL:2	c.134-9863G>C		intron	N/A	ENSP00000474279.1	S4R3F8
ENSG00000298442	ENST00000755524.1		n.179+3285C>G		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000109

AC:

AN:

914864

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

429202

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17686

American (AMR)

AF:

0.00

AC:

AN:

3400

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7640

East Asian (EAS)

AF:

0.00

AC:

AN:

9936

South Asian (SAS)

AF:

0.00

AC:

AN:

18024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2026

European-Non Finnish (NFE)

AF:

0.00000123

AC:

AN:

814616

Other (OTH)

AF:

0.00

AC:

AN:

32158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.1

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.072

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.33

M_CAP

Benign

0.038

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

PhyloP100

0.50

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.84

REVEL

Benign

0.072

Sift

Benign

0.23

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.18

MutPred

0.35

Loss of helix (P = 0.0376)

MVP

0.014

MPC

1.7

ClinPred

0.040

GERP RS

-2.0

Varity_R

0.044

gMVP

0.28

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over