8-144334084-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_031309.6(SCRT1):c.148G>A(p.Val50Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000072 in 1,528,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

SCRT1
NM_031309.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.534

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:

SLC52A2 (HGNC:30224): (solute carrier family 52 member 2) This gene encodes a membrane protein which belongs to the riboflavin transporter family. In humans, riboflavin must be obtained by intestinal absorption because it cannot be synthesized by the body. The water-soluble vitamin riboflavin is processed to the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) which then act as intermediaries in many cellular metabolic reactions. Paralogous members of the riboflavin transporter gene family are located on chromosomes 17 and 20. Unlike other members of this family, this gene has higher expression in brain tissue than small intestine. Alternative splicing of this gene results in multiple transcript variants encoding the same protein. Mutations in this gene have been associated with Brown-Vialetto-Van Laere syndrome 2 - an autosomal recessive progressive neurologic disorder characterized by deafness, bulbar dysfunction, and axial and limb hypotonia. [provided by RefSeq, Jul 2012]

SLC52A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016762614).

BS2

High AC in GnomAd at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCRT1	NM_031309.6 linkuse as main transcript	c.148G>A	p.Val50Ile	missense_variant	2/2	ENST00000569446.3
SCRT1	XM_024447291.2 linkuse as main transcript	c.-54G>A		5_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCRT1	ENST00000569446.3 linkuse as main transcript	c.148G>A	p.Val50Ile	missense_variant	2/2	1	NM_031309.6	P1
SLC52A2	ENST00000675888.1 linkuse as main transcript	c.-138C>T		5_prime_UTR_variant	1/5			P1

Frequencies

GnomAD3 genomes

AF:

0.0000332

AC:

AN:

150616

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000974

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000763

AC:

AN:

131070

Hom.:

AF XY:

0.00

AC XY:

AN XY:

71582

show subpopulations

Gnomad AFR exome

AF:

0.000167

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000435

AC:

AN:

1377846

Hom.:

Cov.:

AF XY:

0.00000294

AC XY:

AN XY:

679898

show subpopulations

Gnomad4 AFR exome

AF:

0.0000984

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:

0.00000187

Gnomad4 OTH exome

AF:

0.0000176

GnomAD4 genome

AF:

0.0000332

AC:

AN:

150616

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73452

show subpopulations

Gnomad4 AFR

AF:

0.0000974

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:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

ESP6500AA

AF:

0.000339

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000210

AC:

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

Feb 06, 2023

The c.148G>A (p.V50I) 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 148, causing the valine (V) at amino acid position 50 to be replaced by an isoleucine (I). 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

0.16

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

Cadd

Benign

Dann

Uncertain

0.97

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-0.060

Sift

Benign

0.46

Sift4G

Benign

0.71

Vest4

0.072

MVP

0.048

ClinPred

0.12

GERP RS

1.2

gMVP

0.22

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