rs79376478

Variant names:

• chr19-46777006-T-C
• rs79376478
• NM_005628.3:c.1357A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-46777006-T-C
• chr19-46777006-T-G

Variant summary

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

The NM_005628.3(SLC1A5):​c.1357A>G​(p.Ile453Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 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. I453L) has been classified as Benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
• Consequence: SLC1A5 NM_005628.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81

Genes affected

SLC1A5 (HGNC:10943): (solute carrier family 1 member 5) The SLC1A5 gene encodes a sodium-dependent neutral amino acid transporter that can act as a receptor for RD114/type D retrovirus (Larriba et al., 2001 [PubMed 11781704]).[supplied by OMIM, Jan 2011]

FKRP (HGNC:17997): (fukutin related protein) This gene encodes a protein which is targeted to the medial Golgi apparatus and is necessary for posttranslational modification of dystroglycan. Mutations in this gene have been associated with congenital muscular dystrophy, cognitive disability, and cerebellar cysts. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Oct 2008]

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=0.2118468).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A5	NM_005628.3	c.1357A>G	p.Ile453Val	missense_variant	Exon 7 of 8	ENST00000542575.6	NP_005619.1
SLC1A5	NM_001145145.2	c.751A>G	p.Ile251Val	missense_variant	Exon 6 of 7		NP_001138617.1
SLC1A5	NM_001145144.2	c.673A>G	p.Ile225Val	missense_variant	Exon 7 of 8		NP_001138616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A5	ENST00000542575.6	c.1357A>G	p.Ile453Val	missense_variant	Exon 7 of 8	1	NM_005628.3	ENSP00000444408.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151892 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

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

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151892 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 74160

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.078	T;.;T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.062
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.9	L;.;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.43	N;N;.;N
REVEL	Benign	0.088
Sift	Benign	0.45	T;T;.;T
Sift4G	Benign	0.47	T;T;T;T
Polyphen		0.14	B;.;.;.
Vest4		0.24
MutPred		0.60		Loss of helix (P = 0.1299);.;.;.;
MVP		0.53
MPC		1.0
ClinPred		0.52	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.046
gMVP		0.71

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: rs79376478; hg19: chr19-47280263;