4-683352-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032219.4(SLC49A3):c.1009G>A(p.Gly337Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC49A3 NM_032219.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.457

Genes affected

SLC49A3 (HGNC:26177): (solute carrier family 49 member 3) Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36386555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC49A3	NM_032219.4	c.1009G>A	p.Gly337Arg	missense_variant	8/10	ENST00000322224.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC49A3	ENST00000322224.9	c.1009G>A	p.Gly337Arg	missense_variant	8/10	1	NM_032219.4	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458490 Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 2 AN XY: 725536

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

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

May 31, 2023

The c.1009G>A (p.G337R) alteration is located in exon 8 (coding exon 8) of the MFSD7 gene. This alteration results from a G to A substitution at nucleotide position 1009, causing the glycine (G) at amino acid position 337 to be replaced by an arginine (R). 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	0.16
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	21
Dann	Uncertain	1.0
Eigen	Benign	0.14
Eigen_PC	Benign	0.019
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.78	T;T;T;T;T;T
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.36	T;T;T;T;T;T
MetaSVM	Benign	-0.36	T
MutationTaster	Benign	0.57	D;D;D;D;D
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.9	D;D;D;D;D;D
REVEL	Benign	0.21
Sift	Benign	0.049	D;T;T;T;T;D
Sift4G	Benign	0.30	T;T;T;T;T;T
Polyphen		0.93	P;P;P;P;D;.
Vest4		0.28
MutPred		0.49		.;.;Loss of catalytic residue at Q337 (P = 0.1198);.;.;.;
MVP		0.59
MPC		0.25
ClinPred		0.90	D
GERP RS		3.6
Varity_R		0.17
gMVP		0.44

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: chr4-677141;