chr8-144509928-C-T

Variant names:

• chr8-144509928-C-T
• rs1009841153
• NM_138431.3:c.595C>T
• SLC33A2 p.Arg199Cys

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

0 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 0 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_SupportingB3_Supporting

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.774
• Publications: 0 publications found

Genes affected

SLC33A2 (HGNC:25157): (solute carrier family 33 member 2) Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be located in plasma membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Jun 2026]

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 0 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Very rare in gnomAD (popmax AF <0.01%) — O3 supporting; GnomAD effective popmax AF = 0.000005 — very rare (O3 supporting [+1])
	B3Computational evidence does not support deleterious effect		Computational evidence does not support a deleterious effect; Missense variant — primary computational scorer does not support an oncogenic/deleterious effect; supports B3

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	Prot: NP_612440.1 UniProt:
	SLC33A2 NR_130120.2		n.859C>T	non_coding_transcript_exon	Exon 1 of 4	Prot:

SLC33A2 NM_138431.3

MANE Select

HGVSc / HGVSpc.595C>Tp.Arg199Cys

Exon rankExon 1 of 5

missense

Prot: NP_612440.1UniProt: Q96ES6

SLC33A2 NR_130120.2

HGVSc / HGVSpn.859C>T

Exon rankExon 1 of 4

non_coding_transcript_exon

Prot:

Ensembl Transcripts

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

MFSD3 ENST00000301327.5

TSL:1MANE Select

HGVSc / HGVSpc.595C>Tp.Arg199Cys

Exon rankExon 1 of 5

missense

Prot: ENSP00000301327.3UniProt: Q96ES6

MFSD3 ENST00000883534.1

HGVSc / HGVSpc.595C>Tp.Arg199Cys

Exon rankExon 1 of 5

missense

Prot: ENSP00000553593.1UniProt: A0ACI8RL54

MFSD3 ENST00000526749.1

TSL:2

HGVSc / HGVSpn.310C>T

Exon rankExon 1 of 2

non_coding_transcript_exon

Prot:

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	AF: 0.0000131	AC:2	Hom:0	AN:152248	Cov:34
GnomAD2 exomes	AF: 0.00000507	AC:1	Hom:	AN:197236	Cov:
GnomAD4 exome	AF: 0.00000560	AC:8	Hom:0	AN:1428472	Cov:31
GnomAD4 genome	AF: 0.0000131	AC:2	Hom:0	AN:152248	Cov:34
TOPMed (Bravo)	AF: 0.00000378	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:0	AN:13470	Cov:
Local & regional cohorts 1 source Population-specific and national genomic databases
Turkish Variome	AF: 0.000207	AC:1	Hom:0	AN:4356	Cov:

Showing 7 sources

Case/control cohorts

Cohort	Cases			Controls
	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

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

Computational Scores

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

Showing 28 of 28 scores

Splicing Scores

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

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.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs1009841153;

hg19: chr8-145735311;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar