Variant 12-53251979-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001170790.2(MFSD5):c.247G>A(p.Ala83Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000697 in 1,391,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

MFSD5
NM_001170790.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.397

Variant links:

Genes affected

MFSD5 (HGNC:28156): (major facilitator superfamily domain containing 5) Predicted to enable molybdate ion transmembrane transporter activity. Predicted to be involved in molybdate ion transport. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

MFSD5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05841908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFSD5	NM_001170790.2 linkuse as main transcript	c.247G>A	p.Ala83Thr	missense_variant	1/2		NP_001164261.1	Q6N075-2
MFSD5	XM_005269197.2 linkuse as main transcript	c.247G>A	p.Ala83Thr	missense_variant	2/3		XP_005269254.1	Q6N075-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFSD5	ENST00000534842.1 linkuse as main transcript	c.247G>A	p.Ala83Thr	missense_variant	1/2	2		ENSP00000442688.1		Q6N075-2
MFSD5	ENST00000551660.2 linkuse as main transcript	c.247G>A	p.Ala83Thr	missense_variant	1/2	2		ENSP00000449354.2		F8VV69

Frequencies

GnomAD3 genomes

AF:

0.0000206

AC:

AN:

145892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000250

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000302

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000654

AC:

AN:

137720

Hom.:

AF XY:

0.0000539

AC XY:

AN XY:

74240

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000816

Gnomad ASJ exome

AF:

0.000120

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000920

Gnomad OTH exome

AF:

0.000240

GnomAD4 exome

AF:

0.0000754

AC:

AN:

1246050

Hom.:

Cov.:

AF XY:

0.0000880

AC XY:

AN XY:

613678

show subpopulations

Gnomad4 AFR exome

AF:

0.0000365

Gnomad4 AMR exome

AF:

0.0000956

Gnomad4 ASJ exome

AF:

0.000101

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000849

Gnomad4 OTH exome

AF:

0.0000619

GnomAD4 genome

AF:

0.0000206

AC:

AN:

145892

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

70912

show subpopulations

Gnomad4 AFR

AF:

0.0000250

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000302

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000144

Hom.:

ExAC

AF:

0.0000446

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.247G>A (p.A83T) alteration is located in exon 1 (coding exon 1) of the MFSD5 gene. This alteration results from a G to A substitution at nucleotide position 247, causing the alanine (A) at amino acid position 83 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

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.19

DANN

Uncertain

0.97

DEOGEN2

Benign

0.0047

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.42

T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.058

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

0.14

N;N

REVEL

Benign

0.0090

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.12

T;T

Vest4

0.054

MutPred

0.20

Gain of glycosylation at A83 (P = 0.0091);Gain of glycosylation at A83 (P = 0.0091);

MVP

0.061

MPC

0.25

ClinPred

0.28

GERP RS

-1.4

gMVP

0.20

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over