20-664314-C-T

Variant names:

• chr20-664314-C-T
• rs1984078380
• NM_033129.4:c.281G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033129.4(SCRT2):​c.281G>A​(p.Arg94His) variant causes a missense change. The variant allele was found at a frequency of 0.000000739 in 1,352,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R94L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: SCRT2 NM_033129.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.80
• 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: 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=0.1344144).

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.281G>A	p.Arg94His	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.281G>A	p.Arg94His	missense	Exon 2 of 2	ENSP00000246104.5	Q9NQ03
	ENSG00000270299	ENST00000488788.2	TSL:2	c.134-9994G>A		intron	N/A	ENSP00000474279.1	S4R3F8
	ENSG00000298442	ENST00000755524.1		n.179+3416C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.39e-7 AC: 1 AN: 1352802 Hom.: 0 Cov.: 33 AF XY: 0.00000149 AC XY: 1 AN XY: 669716

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28728

American (AMR) AF: 0.00 AC: 0 AN: 37310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23564

East Asian (EAS) AF: 0.00 AC: 0 AN: 32382

South Asian (SAS) AF: 0.00 AC: 0 AN: 75178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46986

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5206

European-Non Finnish (NFE) AF: 9.53e-7 AC: 1 AN: 1049086

Other (OTH) AF: 0.00 AC: 0 AN: 54362

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.094	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.8
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.13
Sift	Benign	0.15	T
Sift4G	Benign	0.13	T
Polyphen		0.12	B
Vest4		0.055
MutPred		0.55		Loss of stability (P = 0.0509)
MVP		0.030
MPC		1.4
ClinPred		0.69	D
GERP RS		3.2
Varity_R		0.12
gMVP		0.15
Mutation Taster		=73/27	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: rs1984078380; hg19: chr20-644958;