chr4-2931262-A-C

Position:

• chr4-2931262-A-C

Variant summary

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

The ENST00000355443.9(MFSD10):​c.1127T>G​(p.Val376Gly) variant causes a missense change. 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: 33)
• Consequence: MFSD10 ENST00000355443.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.38

Genes affected

MFSD10 (HGNC:16894): (major facilitator superfamily domain containing 10) This gene encodes a member of the major facilitator superfamily of transporter proteins. The encoded protein likely functions in efflux of organic anions, including the non-steroidal anti-inflammatory drugs indomethacin and diclofenac. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

MFSD10 (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, 0.87

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFSD10	NM_001146069.2	c.1127T>G	p.Val376Gly	missense_variant	11/13	ENST00000355443.9	NP_001139541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFSD10	ENST00000355443.9	c.1127T>G	p.Val376Gly	missense_variant	11/13	1	NM_001146069.2	ENSP00000347619.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Apr 28, 2022

The c.1127T>G (p.V376G) alteration is located in exon 10 (coding exon 10) of the MFSD10 gene. This alteration results from a T to G substitution at nucleotide position 1127, causing the valine (V) at amino acid position 376 to be replaced by a glycine (G). 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	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Benign	0.87
DEOGEN2	Uncertain	0.42	T;T;T
Eigen	Benign	-0.050
Eigen_PC	Benign	-0.051
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.79	T;.;T
M_CAP	Pathogenic	0.68	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Pathogenic	3.5	.;H;H
MutationTaster	Benign	1.0	D;D;D;D;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-6.3	D;D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.64
MutPred		0.63		Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);
MVP		0.52
MPC		0.13
ClinPred		0.98	D
GERP RS		3.6
Varity_R		0.91
gMVP		0.65

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: chr4-2932989;