1-205569086-G-T

Variant names:

• chr1-205569086-G-T
• rs747518493
• NM_181644.5:c.17G>T

Variant summary

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

The NM_181644.5(MFSD4A):​c.17G>T​(p.Arg6Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000745 in 1,342,364 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R6H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: MFSD4A NM_181644.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.50

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-AS1 (HGNC:27632): (MFSD4A antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFSD4A	NM_181644.5	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 10	ENST00000367147.9	NP_857595.3
MFSD4A-AS1	NR_027086.2	n.177+43C>A		intron_variant	Intron 1 of 3
MFSD4A-AS1	NR_152721.1	n.177+43C>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFSD4A	ENST00000367147.9	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 10	1	NM_181644.5	ENSP00000356115.4
MFSD4A	ENST00000489709.5	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 7	5		ENSP00000478732.1
MFSD4A	ENST00000475956.5	n.17G>T		non_coding_transcript_exon_variant	Exon 1 of 8	5		ENSP00000482239.1
MFSD4A	ENST00000539267.5	n.17G>T		non_coding_transcript_exon_variant	Exon 1 of 9	2		ENSP00000445329.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.45e-7 AC: 1 AN: 1342364 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 661084

Gnomad4 AFR exome AF: 0.0000366

Gnomad4 AMR exome AF: 0.00

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: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T;T
Eigen	Benign	0.16
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	T;T
M_CAP	Pathogenic	0.91	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-1.0	T
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.8	D;.
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D;.
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.98	D;.
Vest4		0.38
MutPred		0.57		Loss of methylation at R6 (P = 0.0141);Loss of methylation at R6 (P = 0.0141);
MVP		0.62
MPC		1.4
ClinPred		0.97	D
GERP RS		1.7
Varity_R		0.31
gMVP		0.75

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

Other links and lift over

dbSNP: rs747518493; hg19: chr1-205538214;