Variant 1-205569086-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181644.5(MFSD4A):c.17G>A(p.Arg6His) variant causes a missense change. The variant allele was found at a frequency of 0.00001 in 1,493,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000045 ( 0 hom. )

Consequence

MFSD4A
NM_181644.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.50

Variant links:

Genes affected

MFSD4A (HGNC:25433): (major facilitator superfamily domain containing 4A) Predicted to enable glucose transmembrane transporter activity. Predicted to be involved in glucose transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MFSD4A links:

MFSD4A-AS1 (HGNC:):

MFSD4A-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.10414705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFSD4A	NM_181644.5 linkuse as main transcript	c.17G>A	p.Arg6His	missense_variant	1/10	ENST00000367147.9	NP_857595.3	Q8N468-1Q96KX6
MFSD4A-AS1	NR_027086.2 linkuse as main transcript	n.177+43C>T		intron_variant
MFSD4A-AS1	NR_152721.1 linkuse as main transcript	n.177+43C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MFSD4A	ENST00000367147.9 linkuse as main transcript	c.17G>A	p.Arg6His	missense_variant	1/10	1	NM_181644.5	ENSP00000356115.4	Q8N468-1
MFSD4A	ENST00000489709.5 linkuse as main transcript	c.17G>A	p.Arg6His	missense_variant	1/7	5		ENSP00000478732.1	A0A087WUK7
MFSD4A	ENST00000475956.5 linkuse as main transcript	n.17G>A		non_coding_transcript_exon_variant	1/8	5		ENSP00000482239.1	A0A087WYZ8
MFSD4A	ENST00000539267.5 linkuse as main transcript	n.17G>A		non_coding_transcript_exon_variant	1/9	2		ENSP00000445329.1	F5H391

Frequencies

GnomAD3 genomes

AF:

0.0000529

AC:

AN:

151348

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000363

AC:

AN:

110074

Hom.:

AF XY:

0.0000335

AC XY:

AN XY:

59714

show subpopulations

Gnomad AFR exome

AF:

0.000624

Gnomad AMR exome

AF:

0.000103

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000447

AC:

AN:

1342364

Hom.:

Cov.:

AF XY:

0.00000454

AC XY:

AN XY:

661084

show subpopulations

Gnomad4 AFR exome

AF:

0.000147

Gnomad4 AMR exome

AF:

0.0000328

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000181

GnomAD4 genome

AF:

0.0000594

AC:

AN:

151456

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74004

show subpopulations

Gnomad4 AFR

AF:

0.000217

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000150

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

Jul 09, 2021

The c.17G>A (p.R6H) alteration is located in exon 1 (coding exon 1) of the MFSD4A gene. This alteration results from a G to A substitution at nucleotide position 17, causing the arginine (R) at amino acid position 6 to be replaced by a histidine (H). 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

0.32

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0047

T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.81

T;T

M_CAP

Pathogenic

0.64

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.1

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.4

N;.

REVEL

Benign

0.10

Sift

Benign

0.058

T;.

Sift4G

Benign

0.096

T;T

Polyphen

0.40

B;.

Vest4

0.077

MutPred

0.54

Loss of methylation at R6 (P = 0.0141);Loss of methylation at R6 (P = 0.0141);

MVP

0.38

MPC

0.69

ClinPred

0.071

GERP RS

1.7

Varity_R

0.13

gMVP

0.62

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

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