4-682082-T-G

Variant summary

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

The NM_032219.4(SLC49A3):c.1556A>C(p.Gln519Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000024 in 1,249,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: SLC49A3 NM_032219.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.09

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.073658735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC49A3	NM_032219.4	c.1556A>C	p.Gln519Pro	missense_variant	10/10	ENST00000322224.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC49A3	ENST00000322224.9	c.1556A>C	p.Gln519Pro	missense_variant	10/10	1	NM_032219.4	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000918 AC: 1 AN: 108944 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 60194

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000849

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: 0.00000240 AC: 3 AN: 1249022 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 608972

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000145

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.: 32

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

Jun 22, 2021

The c.1556A>C (p.Q519P) alteration is located in exon 10 (coding exon 10) of the MFSD7 gene. This alteration results from a A to C substitution at nucleotide position 1556, causing the glutamine (Q) at amino acid position 519 to be replaced by a proline (P). 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	0.048
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	1.1
Dann	Benign	0.56
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.39	T;T;T;T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.074	T;T;T;T
MetaSVM	Benign	-0.37	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.080	N;N;N;N
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D;D;D;D
Polyphen		0.0	B;B;B;B
Vest4		0.12
MutPred		0.096		.;.;Gain of glycosylation at Q520 (P = 0.0176);.;
MVP		0.35
MPC		0.097
ClinPred		0.036	T
GERP RS		-2.9
Varity_R		0.087
gMVP		0.085

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs893414506; hg19: chr4-675871;