rs768709238

Variant names:

• chr2-24021732-C-T
• rs768709238
• NM_001346880.2:c.766C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-24021732-C-T
• chr2-24021732-C-A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001346880.2(MFSD2B):​c.766C>T​(p.Arg256Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,613,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: MFSD2B NM_001346880.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.120
• Publications: 0 publications found

Genes affected

MFSD2B (HGNC:37207): (MFSD2 lysolipid transporter B, sphingolipid) Enables sphingolipid transporter activity. Involved in lipid transport. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.4120145).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346880.2. 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
	MFSD2B	NM_001346880.2	MANE Select	c.766C>T	p.Arg256Trp	missense	Exon 7 of 14	NP_001333809.1	A6NFX1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD2B	ENST00000338315.6	TSL:5 MANE Select	c.766C>T	p.Arg256Trp	missense	Exon 7 of 14	ENSP00000342501.4	A6NFX1
	MFSD2B	ENST00000469562.1	TSL:1	n.202C>T		non_coding_transcript_exon	Exon 2 of 8
	MFSD2B	ENST00000669179.1		c.850C>T	p.Arg284Trp	missense	Exon 8 of 15	ENSP00000499689.1	A0A590UK14

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000688 AC: 17 AN: 247242 AF XY: 0.0000522

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000175

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000803

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000146 AC: 214 AN: 1460942 Hom.: 0 Cov.: 32 AF XY: 0.000153 AC XY: 111 AN XY: 726664

African (AFR) AF: 0.0000598 AC: 2 AN: 33468

American (AMR) AF: 0.000135 AC: 6 AN: 44546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39688

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.000164 AC: 182 AN: 1111562

Other (OTH) AF: 0.000298 AC: 18 AN: 60360

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74364

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68032

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000907

ExAC AF: 0.0000414 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.71	D
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.12
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.47
MVP		0.52
MPC		0.36
ClinPred		0.51	D
GERP RS		1.2
Varity_R		0.31
gMVP		0.45
Mutation Taster		=82/18	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: rs768709238; hg19: chr2-24244602;