NM_033129.4:c.407G>C

Variant names:

• chr20-664188-C-G
• rs892177334
• NM_033129.4:c.407G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_033129.4(SCRT2):​c.407G>C​(p.Gly136Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000953 in 146,850 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000095 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCRT2 NM_033129.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.141
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04862991).
• BS2: High AC in GnomAd4 at 14 AD gene.

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.407G>C	p.Gly136Ala	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.407G>C	p.Gly136Ala	missense	Exon 2 of 2	ENSP00000246104.5	Q9NQ03
	ENSG00000270299	ENST00000488788.2	TSL:2	c.134-9868G>C		intron	N/A	ENSP00000474279.1	S4R3F8
	ENSG00000298442	ENST00000755524.1		n.179+3290C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000954 AC: 14 AN: 146746 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000343

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000754 AC: 7 AN: 928598 Hom.: 0 Cov.: 27 AF XY: 0.00000459 AC XY: 2 AN XY: 436104

African (AFR) AF: 0.000222 AC: 4 AN: 18020

American (AMR) AF: 0.00 AC: 0 AN: 3738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8106

East Asian (EAS) AF: 0.00 AC: 0 AN: 11568

South Asian (SAS) AF: 0.00 AC: 0 AN: 18136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2116

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 823380

Other (OTH) AF: 0.0000908 AC: 3 AN: 33052

GnomAD4 genome AF: 0.0000953 AC: 14 AN: 146850 Hom.: 0 Cov.: 32 AF XY: 0.0000560 AC XY: 4 AN XY: 71482

African (AFR) AF: 0.000342 AC: 14 AN: 40984

American (AMR) AF: 0.00 AC: 0 AN: 14782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3398

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66034

Other (OTH) AF: 0.00 AC: 0 AN: 2046

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000132

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	0.13
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.8
DANN	Benign	0.38
DEOGEN2	Benign	0.075	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.14
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	0.47	N
REVEL	Benign	0.011
Sift	Benign	1.0	T
Sift4G	Benign	0.90	T
Polyphen		0.027	B
Vest4		0.16
MutPred		0.49		Gain of relative solvent accessibility (P = 0.0023)
MVP		0.014
MPC		1.3
ClinPred		0.057	T
GERP RS		1.7
Varity_R		0.063
gMVP		0.23
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: rs892177334; hg19: chr20-644832;