NM_031309.6:c.422C>G

Variant names:

• chr8-144333810-G-C
• rs1267114805
• NM_031309.6:c.422C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031309.6(SCRT1):​c.422C>G​(p.Ser141Trp) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S141L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCRT1 NM_031309.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40
• Publications: 0 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: 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=0.19424129).

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.422C>G	p.Ser141Trp	missense	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.422C>G	p.Ser141Trp	missense	Exon 2 of 2	ENSP00000455711.1	Q9BWW7
	SLC52A2	ENST00000675888.1		c.-412G>C		upstream_gene	N/A	ENSP00000502294.1	Q9HAB3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1070464 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 505366

African (AFR) AF: 0.00 AC: 0 AN: 22502

American (AMR) AF: 0.00 AC: 0 AN: 8058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13890

East Asian (EAS) AF: 0.00 AC: 0 AN: 25850

South Asian (SAS) AF: 0.00 AC: 0 AN: 19452

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2888

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 913924

Other (OTH) AF: 0.00 AC: 0 AN: 42896

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Uncertain	24
DANN	Benign	0.97
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.10	N
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.96	T
PhyloP100		2.4
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.4	N
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.0090	D
Vest4		0.33
MutPred		0.36		Loss of glycosylation at S141 (P = 0.0028)
MVP		0.28
ClinPred		0.48	T
GERP RS		1.7
PromoterAI		0.043	Neutral
gMVP		0.24
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1267114805; hg19: chr8-145557472;