NM_001346880.2:c.71C>G

Variant names:

• chr2-24010167-C-G
• rs780620360
• NM_001346880.2:c.71C>G

Variant summary

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

The NM_001346880.2(MFSD2B):​c.71C>G​(p.Pro24Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000772 in 1,294,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. P24Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: MFSD2B NM_001346880.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381
• 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: 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=0.074759245).

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.71C>G	p.Pro24Arg	missense	Exon 1 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.71C>G	p.Pro24Arg	missense	Exon 1 of 14	ENSP00000342501.4	A6NFX1
	MFSD2B	ENST00000669179.1		c.71C>G	p.Pro24Arg	missense	Exon 1 of 15	ENSP00000499689.1	A0A590UK14
	MFSD2B	ENST00000406420.7	TSL:5	c.71C>G	p.Pro24Arg	missense	Exon 1 of 13	ENSP00000385527.3	A0A2I3JL00

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.72e-7 AC: 1 AN: 1294880 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 635690

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26214

American (AMR) AF: 0.00 AC: 0 AN: 24682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22000

East Asian (EAS) AF: 0.00 AC: 0 AN: 28166

South Asian (SAS) AF: 0.0000147 AC: 1 AN: 67868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3774

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1036624

Other (OTH) AF: 0.00 AC: 0 AN: 53626

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.71
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.38
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.0090
Sift	Benign	0.18	T
Sift4G	Benign	0.38	T
Polyphen		0.20	B
Vest4		0.085
MutPred		0.22		Gain of MoRF binding (P = 0.0052)
MVP		0.15
MPC		0.063
ClinPred		0.15	T
GERP RS		1.8
PromoterAI		0.0049	Neutral
Varity_R		0.033
gMVP		0.39
Mutation Taster		=90/10	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: rs780620360; hg19: chr2-24233037;