8-144334001-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_031309.6(SCRT1):c.231G>A(p.Leu77Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00539 in 1,454,890 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 22 hom. )

Consequence

SCRT1
NM_031309.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.78

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 8-144334001-C-T is Benign according to our data. Variant chr8-144334001-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658979.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.78 with no splicing effect.

BS2

High AC in GnomAd4 at 534 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCRT1	NM_031309.6 link	c.231G>A	p.Leu77Leu	synonymous_variant	Exon 2 of 2	ENST00000569446.3	NP_112599.2	Q9BWW7
SCRT1	XM_024447291.2 link	c.30G>A	p.Leu10Leu	synonymous_variant	Exon 2 of 2		XP_024303059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCRT1	ENST00000569446.3 link	c.231G>A	p.Leu77Leu	synonymous_variant	Exon 2 of 2	1	NM_031309.6	ENSP00000455711.1		Q9BWW7
SLC52A2	ENST00000675888.1 link	c.-221C>T		5_prime_UTR_variant	Exon 1 of 5			ENSP00000502294.1		Q9HAB3

Frequencies

GnomAD3 genomes

AF:

0.00351

AC:

534

AN:

151994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00636

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00304

AC:

224

AN:

73716

AF XY:

0.00274

show subpopulations

Gnomad AFR exome

AF:

0.000840

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.00577

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000806

Gnomad NFE exome

AF:

0.00612

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00561

AC:

7308

AN:

1302788

Hom.:

Cov.:

AF XY:

0.00556

AC XY:

3545

AN XY:

637826

show subpopulations

African (AFR)

AF:

0.000841

AC:

AN:

26164

American (AMR)

AF:

0.00197

AC:

AN:

25374

Ashkenazi Jewish (ASJ)

AF:

0.00533

AC:

119

AN:

22312

East Asian (EAS)

AF:

0.0000348

AC:

AN:

28696

South Asian (SAS)

AF:

0.000347

AC:

AN:

72008

European-Finnish (FIN)

AF:

0.00244

AC:

AN:

34034

Middle Eastern (MID)

AF:

0.00102

AC:

AN:

3920

European-Non Finnish (NFE)

AF:

0.00655

AC:

6788

AN:

1036578

Other (OTH)

AF:

0.00402

AC:

216

AN:

53702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

371

743

1114

1486

1857

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00351

AC:

534

AN:

152102

Hom.:

Cov.:

AF XY:

0.00296

AC XY:

220

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

41522

American (AMR)

AF:

0.00137

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00123

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00636

AC:

432

AN:

67924

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

101

135

169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00422

Hom.:

Bravo

AF:

0.00346

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SCRT1: BP4, BP7, BS2; SLC52A2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

2.8

PromoterAI

0.0058

Neutral

(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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8-144334001-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over