20-664183-C-G

Variant summary

Our verdict is Likely benign. Variant got -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. 14/21 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

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.501
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.065972745).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SCRT2NM_033129.4 linkc.412G>C p.Ala138Pro missense_variant Exon 2 of 2 ENST00000246104.7 NP_149120.1 Q9NQ03

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SCRT2ENST00000246104.7 linkc.412G>C p.Ala138Pro missense_variant Exon 2 of 2 1 NM_033129.4 ENSP00000246104.5 Q9NQ03
ENSG00000270299ENST00000488788.2 linkc.134-9863G>C intron_variant Intron 1 of 2 2 ENSP00000474279.1 S4R3F8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000109
AC:
1
AN:
914864
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
429202
show subpopulations
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:
0.00000123
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 06, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.412G>C (p.A138P) alteration is located in exon 2 (coding exon 2) of the SCRT2 gene. This alteration results from a G to C substitution at nucleotide position 412, causing the alanine (A) at amino acid position 138 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
7.1
DANN
Benign
0.85
DEOGEN2
Benign
0.072
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.33
T
M_CAP
Benign
0.038
D
MetaRNN
Benign
0.066
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.0
N
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
0.84
N
REVEL
Benign
0.072
Sift
Benign
0.23
T
Sift4G
Benign
0.34
T
Polyphen
0.0
B
Vest4
0.18
MutPred
0.35
Loss of helix (P = 0.0376);
MVP
0.014
MPC
1.7
ClinPred
0.040
T
GERP RS
-2.0
Varity_R
0.044
gMVP
0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-644827; API