Genetic Variant SCRT1:p.Leu77Leu (chr8-144334001-C-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_031309.6(SCRT1):c.231G>C(p.Leu77Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000768 in 1,302,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L77L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

SCRT1
NM_031309.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.78

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP7

Synonymous conserved (PhyloP=2.78 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCRT1	NM_031309.6 link	c.231G>C	p.Leu77Leu	synonymous_variant	Exon 2 of 2	ENST00000569446.3	NP_112599.2	Q9BWW7
SCRT1	XM_024447291.2 link	c.30G>C	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>C	p.Leu77Leu	synonymous_variant	Exon 2 of 2	1	NM_031309.6	ENSP00000455711.1		Q9BWW7
SLC52A2	ENST00000675888.1 link	c.-221C>G		5_prime_UTR_variant	Exon 1 of 5			ENSP00000502294.1		Q9HAB3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.68e-7

AC:

AN:

1302802

Hom.:

Cov.:

AF XY:

0.00000157

AC XY:

AN XY:

637834

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26164

American (AMR)

AF:

0.00

AC:

AN:

25374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22312

East Asian (EAS)

AF:

0.00

AC:

AN:

28696

South Asian (SAS)

AF:

0.00

AC:

AN:

72008

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34034

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3920

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1036592

Other (OTH)

AF:

0.0000186

AC:

AN:

53702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.36

PhyloP100

2.8

PromoterAI

-0.0018

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-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over