chr17-76744344-T-G

Position:

• chr17-76744344-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001242532.5(MFSD11):​c.519T>G​(p.Phe173Leu) variant causes a missense change involving the alteration of a non-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: 32)
• Consequence: MFSD11 NM_001242532.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.102

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]

MFSD11 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.812

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFSD11	NM_001242532.5	c.519T>G	p.Phe173Leu	missense_variant	7/13	ENST00000685175.1	NP_001229461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFSD11	ENST00000685175.1	c.519T>G	p.Phe173Leu	missense_variant	7/13		NM_001242532.5	ENSP00000508960.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2022

The c.519T>G (p.F173L) alteration is located in exon 7 (coding exon 7) of the MFSD11 gene. This alteration results from a T to G substitution at nucleotide position 519, causing the phenylalanine (F) at amino acid position 173 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	0.99
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.29
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;T;T;.;.;T;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.94	.;.;D;D;.;.;.
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.81	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.31	D
MutationAssessor	Pathogenic	2.9	M;M;M;.;.;M;M
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-4.3	.;.;.;D;.;D;.
REVEL	Uncertain	0.56
Sift	Uncertain	0.0060	.;.;.;D;.;D;.
Sift4G	Uncertain	0.016	D;D;D;T;T;D;D
Polyphen		0.95	P;P;P;D;D;P;P
Vest4		0.90
MutPred		0.41		Loss of helix (P = 0.2022);Loss of helix (P = 0.2022);Loss of helix (P = 0.2022);.;.;Loss of helix (P = 0.2022);Loss of helix (P = 0.2022);
MVP		0.58
MPC		1.1
ClinPred		1.0	D
GERP RS		-6.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.64
gMVP		0.88

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

LitVar

Other links and lift over

dbSNP: rs2078362859; hg19: chr17-74740426;