Genetic Variant NM_031309.6:c.90C>G (chr8-144336080-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031309.6(SCRT1):c.90C>G(p.Asp30Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

SCRT1
NM_031309.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.624

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Brown-Vialetto-van Laere syndrome 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P

SLC52A2 links:

ENSG00000307714 (HGNC:):

ENSG00000307714 links:

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ACMG classification

Classification was made for transcript

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=0.07867813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCRT1	NM_031309.6 link	c.90C>G	p.Asp30Glu	missense_variant	Exon 1 of 2	ENST00000569446.3	NP_112599.2	Q9BWW7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCRT1	ENST00000569446.3 link	c.90C>G	p.Asp30Glu	missense_variant	Exon 1 of 2	1	NM_031309.6	ENSP00000455711.1	Q9BWW7
SLC52A2	ENST00000675888.1 link	c.-111+1969G>C		intron_variant	Intron 1 of 4			ENSP00000502294.1	Q9HAB3
ENSG00000307714	ENST00000828084.1 link	n.224+501G>C		intron_variant	Intron 1 of 1
ENSG00000307714	ENST00000828085.1 link	n.340+369G>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.38

M_CAP

Benign

0.011

MetaRNN

Benign

0.079

MetaSVM

Benign

-0.92

PhyloP100

0.62

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.67

Sift

Benign

0.31

Sift4G

Benign

0.17

Vest4

0.046

MutPred

0.17

Gain of helix (P = 0.0696);

MVP

0.15

ClinPred

0.46

GERP RS

2.1

PromoterAI

-0.072

Neutral

(source)

gMVP

0.091

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over