19-46787917-G-C

Variant names:

• chr19-46787917-G-C
• rs3027956
• NM_005628.3:c.49C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005628.3(SLC1A5):​c.49C>G​(p.Pro17Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,572,014 control chromosomes in the GnomAD database, including 37,190 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.18 (2993 hom., cov: 33)
  • Exomes 𝑓: 0.21 (34197 hom.)
• Consequence: SLC1A5 NM_005628.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640

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]

ENSG00000275719 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.6063452E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A5	NM_005628.3	c.49C>G	p.Pro17Ala	missense_variant	Exon 1 of 8	ENST00000542575.6	NP_005619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A5	ENST00000542575.6	c.49C>G	p.Pro17Ala	missense_variant	Exon 1 of 8	1	NM_005628.3	ENSP00000444408.1
ENSG00000275719	ENST00000612522.1	n.103G>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000275719	ENST00000617006.1	n.103G>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26831 AN: 152128 Hom.: 2990 Cov.: 33

Gnomad AFR AF: 0.0607

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.198

GnomAD3 exomes AF: 0.191 AC: 34413 AN: 180080 Hom.: 3974 AF XY: 0.189 AC XY: 18880 AN XY: 99984

Gnomad AFR exome AF: 0.0449

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.170

Gnomad EAS exome AF: 0.478

Gnomad SAS exome AF: 0.131

Gnomad FIN exome AF: 0.198

Gnomad NFE exome AF: 0.196

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.212 AC: 301444 AN: 1419768 Hom.: 34197 Cov.: 34 AF XY: 0.210 AC XY: 147415 AN XY: 702984

Gnomad4 AFR exome AF: 0.0519

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.443

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.209

Gnomad4 NFE exome AF: 0.218

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.176 AC: 26836 AN: 152246 Hom.: 2993 Cov.: 33 AF XY: 0.176 AC XY: 13113 AN XY: 74436

Gnomad4 AFR AF: 0.0606

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.204

Alfa AF: 0.196 Hom.: 958

Bravo AF: 0.171

TwinsUK AF: 0.206 AC: 762

ALSPAC AF: 0.208 AC: 803

ESP6500AA AF: 0.0211 AC: 63

ESP6500EA AF: 0.0926 AC: 595

ExAC AF: 0.140 AC: 15566

Asia WGS AF: 0.291 AC: 1011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.7
DANN	Benign	0.97
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.00016	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.070
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.020	D
Polyphen		0.10	B
Vest4		0.052
MPC		0.56
ClinPred		0.0078	T
GERP RS		2.1
Varity_R		0.021
gMVP		0.39

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: rs3027956; hg19: chr19-47291174; COSMIC: COSV69467084; COSMIC: COSV69467084;