17-76742024-G-T

Variant names:

• chr17-76742024-G-T
• NM_001242532.5:c.316G>T

Variant summary

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

The NM_001242532.5(MFSD11):​c.316G>T​(p.Val106Phe) 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: 32)
• Consequence: MFSD11 NM_001242532.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.56

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

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, 0.865

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFSD11	NM_001242532.5	c.316G>T	p.Val106Phe	missense_variant	Exon 4 of 13	ENST00000685175.1	NP_001229461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFSD11	ENST00000685175.1	c.316G>T	p.Val106Phe	missense_variant	Exon 4 of 13		NM_001242532.5	ENSP00000508960.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.316G>T (p.V106F) alteration is located in exon 4 (coding exon 4) of the MFSD11 gene. This alteration results from a G to T substitution at nucleotide position 316, causing the valine (V) at amino acid position 106 to be replaced by a phenylalanine (F). 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	Benign	0.32
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T;T;T;.;.;.;T;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	.;.;D;D;D;.;.;.
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.87	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.11	D
MutationAssessor	Uncertain	2.5	M;M;M;M;.;M;M;M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.5	.;.;.;D;.;.;D;.
REVEL	Pathogenic	0.79
Sift	Uncertain	0.0060	.;.;.;D;.;.;D;.
Sift4G	Benign	0.10	T;T;T;D;T;D;T;T
Polyphen		0.078	B;B;B;P;.;P;B;B
Vest4		0.96
MutPred		0.63		Loss of stability (P = 0.2896);Loss of stability (P = 0.2896);Loss of stability (P = 0.2896);Loss of stability (P = 0.2896);Loss of stability (P = 0.2896);Loss of stability (P = 0.2896);Loss of stability (P = 0.2896);Loss of stability (P = 0.2896);
MVP		0.91
MPC		0.73
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.64
gMVP		0.96

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: chr17-74738106;