chr20-664183-C-G

Variant names:

• chr20-664183-C-G
• rs2122341523
• NM_033129.4:c.412G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.501
• Publications: 0 publications found

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]

ENSG00000270299 (HGNC:):

ACMG classification

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

Sel.	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.: 32

GnomAD4 exome AF: 0.00000109 AC: 1 AN: 914864 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 429202

African (AFR) AF: 0.00 AC: 0 AN: 17686

American (AMR) AF: 0.00 AC: 0 AN: 3400

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7640

East Asian (EAS) AF: 0.00 AC: 0 AN: 9936

South Asian (SAS) AF: 0.00 AC: 0 AN: 18024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2026

European-Non Finnish (NFE) AF: 0.00000123 AC: 1 AN: 814616

Other (OTH) AF: 0.00 AC: 0 AN: 32158

GnomAD4 genome Cov.: 32

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	0.11
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
PhyloP100		0.50
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
Mutation Taster		=92/8	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: rs2122341523; hg19: chr20-644827;