8-144509545-C-T

Position:

• chr8-144509545-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138431.3(MFSD3):​c.212C>T​(p.Thr71Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000219 in 1,367,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: MFSD3 NM_138431.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.928

Genes affected

MFSD3 (HGNC:25157): (major facilitator superfamily domain containing 3) Predicted to enable solute:proton symporter activity. Predicted to be involved in proton transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MFSD3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09357914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFSD3	NM_138431.3	c.212C>T	p.Thr71Met	missense_variant	1/5	ENST00000301327.5	NP_612440.1
MFSD3	XM_017013005.2	c.212C>T	p.Thr71Met	missense_variant	1/4		XP_016868494.1
MFSD3	XM_011516806.3	c.212C>T	p.Thr71Met	missense_variant	1/5		XP_011515108.1
MFSD3	NR_130120.2	n.476C>T		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFSD3	ENST00000301327.5	c.212C>T	p.Thr71Met	missense_variant	1/5	1	NM_138431.3	ENSP00000301327.3
MFSD3	ENST00000528047.5	n.466C>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000219 AC: 3 AN: 1367670 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 674578

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000130

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000186

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

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

Oct 05, 2022

The c.212C>T (p.T71M) alteration is located in exon 1 (coding exon 1) of the MFSD3 gene. This alteration results from a C to T substitution at nucleotide position 212, causing the threonine (T) at amino acid position 71 to be replaced by a methionine (M). 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	0.17
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.9
DANN	Benign	0.89
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.054
Sift	Benign	0.22	T
Sift4G	Benign	0.098	T
Polyphen		0.17	B
Vest4		0.068
MutPred		0.53		Loss of sheet (P = 0.0084);
MVP		0.28
MPC		1.3
ClinPred		0.081	T
GERP RS		-0.89
Varity_R		0.040
gMVP		0.33

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: chr8-145734928;