17-76740985-G-A

Variant names:

• chr17-76740985-G-A
• NM_001242532.5:c.181G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001242532.5(MFSD11):​c.181G>A​(p.Ala61Thr) 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 benign 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: 7.62

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39039117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFSD11	NM_001242532.5	c.181G>A	p.Ala61Thr	missense_variant	Exon 3 of 13	ENST00000685175.1	NP_001229461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFSD11	ENST00000685175.1	c.181G>A	p.Ala61Thr	missense_variant	Exon 3 of 13		NM_001242532.5	ENSP00000508960.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.181G>A (p.A61T) alteration is located in exon 3 (coding exon 3) of the MFSD11 gene. This alteration results from a G to A substitution at nucleotide position 181, causing the alanine (A) at amino acid position 61 to be replaced by a threonine (T). 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	0.12
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T;T;T;.;.;.;.;T;T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	.;.;D;D;D;D;.;.;.
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.39	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.5	L;L;L;L;.;.;L;L;L
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.82	.;.;.;N;.;.;.;N;.
REVEL	Uncertain	0.32
Sift	Benign	0.14	.;.;.;T;.;.;.;T;.
Sift4G	Benign	0.12	T;T;T;T;T;T;T;T;T
Polyphen		0.031	B;B;B;P;.;.;P;B;B
Vest4		0.52
MutPred		0.40		Gain of glycosylation at T66 (P = 0.1395);Gain of glycosylation at T66 (P = 0.1395);Gain of glycosylation at T66 (P = 0.1395);Gain of glycosylation at T66 (P = 0.1395);Gain of glycosylation at T66 (P = 0.1395);Gain of glycosylation at T66 (P = 0.1395);Gain of glycosylation at T66 (P = 0.1395);Gain of glycosylation at T66 (P = 0.1395);Gain of glycosylation at T66 (P = 0.1395);
MVP		0.77
MPC		0.53
ClinPred		0.72	D
GERP RS		5.8
Varity_R		0.16
gMVP		0.68

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: chr17-74737067;