chr8-144334001-C-T

Variant names:

• chr8-144334001-C-T
• rs544319039
• NM_031309.6:c.231G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.78
• Publications: 1 publications found

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]

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, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp

ACMG classification

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031309.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCRT1	NM_031309.6	MANE Select	c.231G>A	p.Leu77Leu	synonymous	Exon 2 of 2	NP_112599.2	Q9BWW7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCRT1	ENST00000569446.3	TSL:1 MANE Select	c.231G>A	p.Leu77Leu	synonymous	Exon 2 of 2	ENSP00000455711.1	Q9BWW7
	SLC52A2	ENST00000675888.1		c.-221C>T		5_prime_UTR	Exon 1 of 5	ENSP00000502294.1	Q9HAB3

Frequencies

GnomAD3 genomes AF: 0.00351 AC: 534 AN: 151994 Hom.: 2 Cov.: 32

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

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.: 22 Cov.: 32 AF XY: 0.00556 AC XY: 3545 AN XY: 637826

African (AFR) AF: 0.000841 AC: 22 AN: 26164

American (AMR) AF: 0.00197 AC: 50 AN: 25374

Ashkenazi Jewish (ASJ) AF: 0.00533 AC: 119 AN: 22312

East Asian (EAS) AF: 0.0000348 AC: 1 AN: 28696

South Asian (SAS) AF: 0.000347 AC: 25 AN: 72008

European-Finnish (FIN) AF: 0.00244 AC: 83 AN: 34034

Middle Eastern (MID) AF: 0.00102 AC: 4 AN: 3920

European-Non Finnish (NFE) AF: 0.00655 AC: 6788 AN: 1036578

Other (OTH) AF: 0.00402 AC: 216 AN: 53702

GnomAD4 genome AF: 0.00351 AC: 534 AN: 152102 Hom.: 2 Cov.: 32 AF XY: 0.00296 AC XY: 220 AN XY: 74354

African (AFR) AF: 0.00108 AC: 45 AN: 41522

American (AMR) AF: 0.00137 AC: 21 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00123 AC: 13 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00636 AC: 432 AN: 67924

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00422 Hom.: 1

Bravo AF: 0.00346

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.88
PhyloP100		2.8
PromoterAI		0.0058	Neutral

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

Other links and lift over

dbSNP: rs544319039; hg19: chr8-145557663; COSMIC: COSV59780935;