8-144354670-G-C

Variant names:

• chr8-144354670-G-C
• rs370391854
• NM_001280561.2:c.98C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001280561.2(CATSPERQ):​c.98C>G​(p.Ala33Gly) 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. 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. A33V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CATSPERQ NM_001280561.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.43
• Publications: 0 publications found

Genes affected

CATSPERQ (HGNC:44155): (transmembrane protein 249) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000271698 (HGNC:):

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.269664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CATSPERQ	NM_001280561.2	c.98C>G	p.Ala33Gly	missense_variant	Exon 2 of 6	ENST00000696146.1	NP_001267490.1
CATSPERQ	NM_001252402.3	c.98C>G	p.Ala33Gly	missense_variant	Exon 1 of 5		NP_001239331.1
CATSPERQ	NM_001252404.3	c.98C>G	p.Ala33Gly	missense_variant	Exon 1 of 4		NP_001239333.1
CATSPERQ	NR_047684.3	n.262C>G		non_coding_transcript_exon_variant	Exon 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM249	ENST00000696146.1	c.98C>G	p.Ala33Gly	missense_variant	Exon 2 of 6		NM_001280561.2	ENSP00000512438.1
ENSG00000271698	ENST00000531225.1	n.*787C>G		non_coding_transcript_exon_variant	Exon 2 of 6	2		ENSP00000436572.2
ENSG00000271698	ENST00000531225.1	n.*787C>G		3_prime_UTR_variant	Exon 2 of 6	2		ENSP00000436572.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	0.0062	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.63	D
M_CAP	Pathogenic	0.34	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	2.0	M;.
PhyloP100		3.4
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.0	N;D
Sift	Benign	0.56	T;D
Sift4G	Pathogenic	0.0	D;.
Polyphen		1.0	D;.
Vest4		0.39
MutPred		0.29		Gain of relative solvent accessibility (P = 0.0023);Gain of relative solvent accessibility (P = 0.0023);
MVP		0.067
ClinPred		0.69	D
GERP RS		4.1
PromoterAI		0.016	Neutral
Varity_R		0.16
gMVP		0.20
Mutation Taster		=100/0	polymorphism

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: rs370391854; hg19: chr8-145578330;