rs780360874

Variant names:

• chr17-76742230-A-C
• rs780360874
• NM_001242532.5:c.394A>C

Your query was ambiguous. Multiple possible variants found:

• chr17-76742230-A-C
• chr17-76742230-A-G

Variant summary

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

The NM_001242532.5(MFSD11):​c.394A>C​(p.Ile132Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. I132V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MFSD11 NM_001242532.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.91
• Publications: 0 publications found

Genes affected

MFSD11 (HGNC:25458): (major facilitator superfamily domain containing 11) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242532.5. 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
	MFSD11	NM_001242532.5	MANE Select	c.394A>C	p.Ile132Leu	missense	Exon 5 of 13	NP_001229461.1	O43934-1
	MFSD11	NM_001242533.3		c.394A>C	p.Ile132Leu	missense	Exon 6 of 14	NP_001229462.1	O43934-1
	MFSD11	NM_001242534.3		c.394A>C	p.Ile132Leu	missense	Exon 6 of 14	NP_001229463.1	O43934-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD11	ENST00000685175.1	MANE Select	c.394A>C	p.Ile132Leu	missense	Exon 5 of 13	ENSP00000508960.1	O43934-1
	MFSD11	ENST00000336509.8	TSL:1	c.394A>C	p.Ile132Leu	missense	Exon 6 of 14	ENSP00000337240.3	O43934-1
	MFSD11	ENST00000590514.5	TSL:1	c.394A>C	p.Ile132Leu	missense	Exon 6 of 14	ENSP00000468309.1	O43934-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Uncertain	-0.28	T
PhyloP100		8.9
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.81	N
REVEL	Uncertain	0.42
Sift	Uncertain	0.025	D
Sift4G	Benign	0.43	T
Polyphen		0.15	B
Vest4		0.59
MutPred		0.63		Gain of catalytic residue at I132 (P = 0.1338)
MVP		0.54
MPC		0.57
ClinPred		0.99	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.57
Mutation Taster		=38/62	disease causing

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: rs780360874; hg19: chr17-74738312;