Genetic Variant SCRT2:p.Ala138Thr (chr20-664183-C-T) – 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>A(p.Ala138Thr) 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. 15/22 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. A138G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SCRT2
NM_033129.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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=0.06388885).

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>A	p.Ala138Thr	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>A	p.Ala138Thr	missense	Exon 2 of 2	ENSP00000246104.5	Q9NQ03
ENSG00000270299	ENST00000488788.2	TSL:2	c.134-9863G>A		intron	N/A	ENSP00000474279.1	S4R3F8
ENSG00000298442	ENST00000755524.1		n.179+3285C>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

914864

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

429202

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:

0.00

AC:

AN:

814616

Other (OTH)

AF:

0.00

AC:

AN:

32158

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.72

CADD

Benign

7.4

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.074

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.32

M_CAP

Benign

0.039

MetaRNN

Benign

0.064

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

PhyloP100

0.50

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.82

REVEL

Benign

0.049

Sift

Benign

0.16

Sift4G

Benign

0.59

Polyphen

0.0

Vest4

0.10

MutPred

0.28

Loss of helix (P = 0.0376)

MVP

0.014

MPC

1.1

ClinPred

0.043

GERP RS

-2.0

Varity_R

0.034

gMVP

0.17

Mutation Taster

=96/4

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