17-76738404-T-C

Variant names:

• chr17-76738404-T-C
• NM_001242532.5:c.52T>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001242532.5(MFSD11):​c.52T>C​(p.Phe18Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: MFSD11 NM_001242532.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.36

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]

ENSG00000267168 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.923

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFSD11	NM_001242532.5	c.52T>C	p.Phe18Leu	missense_variant	Exon 1 of 13	ENST00000685175.1	NP_001229461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFSD11	ENST00000685175.1	c.52T>C	p.Phe18Leu	missense_variant	Exon 1 of 13		NM_001242532.5	ENSP00000508960.1
ENSG00000267168	ENST00000587459.1	c.*58T>C		3_prime_UTR_variant	Exon 2 of 2	5		ENSP00000466829.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 19, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.52T>C (p.F18L) alteration is located in exon 1 (coding exon 1) of the MFSD11 gene. This alteration results from a T to C substitution at nucleotide position 52, causing the phenylalanine (F) at amino acid position 18 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.40
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.25	T;T;T;.;.;.;.;.;.;T;T
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	.;.;D;.;D;D;D;D;.;.;.
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.92	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.69	D
MutationAssessor	Pathogenic	3.5	M;M;M;.;.;M;.;.;M;M;M
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-5.4	.;.;.;.;.;D;.;.;.;D;.
REVEL	Pathogenic	0.90
Sift	Pathogenic	0.0	.;.;.;.;.;D;.;.;.;D;.
Sift4G	Uncertain	0.010	D;D;D;D;D;D;D;D;D;D;D
Polyphen		1.0	D;D;D;.;.;D;.;.;D;D;D
Vest4		0.96
MutPred		0.76		Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);
MVP		0.88
MPC		1.2
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.96
gMVP		0.89

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-74734486;