Variant 8-144333696-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031309.6(SCRT1):c.536G>A(p.Arg179His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000357 in 1,399,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

SCRT1
NM_031309.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.243

Variant links:

Genes affected

SCRT1 (HGNC:15950): (scratch family transcriptional repressor 1) This gene encodes a C2H2-type zinc finger transcriptional repressor that binds to E-box motifs. The encoded protein may promote neural differention and may be involved in cancers with neuroendocrine features. [provided by RefSeq, Jul 2013]

SCRT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11483204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCRT1	NM_031309.6 linkuse as main transcript	c.536G>A	p.Arg179His	missense_variant	2/2	ENST00000569446.3	NP_112599.2
SCRT1	XM_024447291.2 linkuse as main transcript	c.335G>A	p.Arg112His	missense_variant	2/2		XP_024303059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCRT1	ENST00000569446.3 linkuse as main transcript	c.536G>A	p.Arg179His	missense_variant	2/2	1	NM_031309.6	ENSP00000455711	P1

Frequencies

GnomAD3 genomes

AF:

0.0000135

AC:

AN:

147894

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000489

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

AF:

0.00000240

AC:

AN:

1252082

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

611780

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:

0.0000297

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000390

GnomAD4 genome

AF:

0.0000135

AC:

AN:

147894

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72032

show subpopulations

Gnomad4 AFR

AF:

0.0000489

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.536G>A (p.R179H) alteration is located in exon 2 (coding exon 2) of the SCRT1 gene. This alteration results from a G to A substitution at nucleotide position 536, causing the arginine (R) at amino acid position 179 to be replaced by a histidine (H). 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

0.28

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.39

M_CAP

Benign

0.046

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.39

Sift

Benign

0.14

Sift4G

Benign

0.38

Vest4

0.12

MutPred

0.35

Loss of MoRF binding (P = 0.0093);

MVP

0.088

ClinPred

0.24

GERP RS

1.1

gMVP

0.21

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over