chr17-76741994-C-T

Variant names:

• chr17-76741994-C-T
• NM_001242532.5:c.286C>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.286C>T​(p.Pro96Ser) 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: 7.53

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, 0.9

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFSD11	NM_001242532.5	c.286C>T	p.Pro96Ser	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.286C>T	p.Pro96Ser	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

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.286C>T (p.P96S) alteration is located in exon 4 (coding exon 4) of the MFSD11 gene. This alteration results from a C to T substitution at nucleotide position 286, causing the proline (P) at amino acid position 96 to be replaced by a serine (S). 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	0.83
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.24	T;T;T;.;.;.;T;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.86	.;.;D;D;D;.;.;.
M_CAP	Benign	0.040	D
MetaRNN	Pathogenic	0.90	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.9	M;M;M;M;.;M;M;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-6.5	.;.;.;D;.;.;D;.
REVEL	Uncertain	0.42
Sift	Benign	0.031	.;.;.;D;.;.;D;.
Sift4G	Uncertain	0.042	D;D;D;T;D;T;D;D
Polyphen		0.68	P;P;P;D;.;D;P;P
Vest4		0.91
MutPred		0.77		Loss of catalytic residue at P96 (P = 0.1953);Loss of catalytic residue at P96 (P = 0.1953);Loss of catalytic residue at P96 (P = 0.1953);Loss of catalytic residue at P96 (P = 0.1953);Loss of catalytic residue at P96 (P = 0.1953);Loss of catalytic residue at P96 (P = 0.1953);Loss of catalytic residue at P96 (P = 0.1953);Loss of catalytic residue at P96 (P = 0.1953);
MVP		0.62
MPC		1.0
ClinPred		1.0	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr17-74738076;