NM_138431.3:c.595C>T

Variant names:

Variant summary

Our verdict is The variant received 1 classification points (ACMG Germline Pathogenicity v2019). PM2BP4

The NM_138431.3(SLC33A2):c.595C>T (p.Arg199Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.00000633 (AC=10) in the gnomAD database across 1,580,720 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.00000488. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

SLC33A2
NM_138431.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.774

Publications

0 publications found

Variant links:

Genes affected

SLC33A2 (HGNC:25157): (major facilitator superfamily domain containing 3) Predicted to enable solute:proton symporter activity. Predicted to be involved in proton transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC33A2 links:

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new If you want to explore the variant's impact on the transcript NM_138431.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 points.

PM2

Very rare in gnomAD for AR/unknown gene (popmax AF < threshold/10) — PM2; GnomAD popmax AF = 0.00000488 — very rare for unknown gene (threshold 0.001) — PM2 moderate.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Supporting).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_138431.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC33A2	NM_138431.3	MANE Select	c.595C>T	p.Arg199Cys	missense	Exon 1 of 5	NP_612440.1	Q96ES6
	SLC33A2	NR_130120.2		n.859C>T		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MFSD3	ENST00000301327.5	TSL:1 MANE Select	c.595C>T	p.Arg199Cys	missense	Exon 1 of 5	ENSP00000301327.3	Q96ES6
MFSD3	ENST00000883534.1		c.595C>T	p.Arg199Cys	missense	Exon 1 of 5	ENSP00000553593.1	A0ACI8RL54
MFSD3	ENST00000526749.1	TSL:2	n.310C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	0.0000131	2	0	152248	34
GnomAD2 exomes	0.00000507	1		197236
GnomAD4 exome	0.00000560	8	0	1428472	31
GnomAD4 genome	0.0000131	2	0	152248	34
TOPMed (Bravo)	0.00000378
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	0.00	0	0	13470
Local & regional cohorts 1 source Population-specific and national genomic databases
Turkish Variome	0.000207	1	0	4356

Showing 7 sources

Case/control cohorts

Cohort	Cases			Controls
Cohort	AF	AC	AN	AF	AC	AN
SCHEMA (Schizophrenia)	0.00	0	65664	0.0000311	4	128814

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
AlphaGenome AVI	Benign	-	7.8
AlphaMissense	Benign	-	0.20
BayesDel_addAF	Benign	T	-0.13
BayesDel_noAF	Benign	-	-0.42
CADD	Benign	-	17
DANN	Uncertain	-	1.0
DEOGEN2	Benign	T	0.35
Eigen	Benign	-	-0.50
Eigen_PC	Benign	-	-0.67
FATHMM_MKL	Benign	N	0.12
FuncVEP CTI	Benign	-	0.14
GPN-Star LLR	N/A	-	-2.1
GPN-Star score	N/A	-	2.1
LIST_S2	Benign	T	0.59
M_CAP	Uncertain	D	0.12
MetaRNN	Benign	T	0.24
MetaSVM	Benign	T	-0.63
Mutation Taster	N/A	polymorphism	95/5
MutationAssessor	Benign	L	1.7
PhyloP100	Benign	-	-0.77
popEVE	Benign	-	-3.2
PrimateAI	Benign	T	0.42
PROVEAN	Benign	N	-1.8
REVEL	Benign	-	0.26
Sift	Benign	T	0.063
Sift4G	Uncertain	D	0.012
Varity_R	N/A	-	0.18
VESM-3B	Benign	-	-6.2

Showing 28 of 28 scores

Splicing Scores

Algorithm	Calibrated prediction	Prediction	Score
Pangolin (max)	Benign	-	0.010
SpliceAI score (max)	Benign	- Details are displayed if max score is > 0.2	0.020

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Case/control cohorts

ClinVar

Computational Scores

Splicing Scores

Publications

Other links and lift over