5-151467200-C-G

Variant names:

• chr5-151467200-C-G
• rs35204299
• NM_078483.4:c.421C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_078483.4(SLC36A1):​c.421C>G​(p.Arg141Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,607,672 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R141C) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: SLC36A1 NM_078483.4 missense, splice_region
• Scores: Splicing: ADA: 0.002966
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.68
• Publications: 4 publications found

Genes affected

SLC36A1 (HGNC:18761): (solute carrier family 36 member 1) This gene encodes a member of the eukaryote-specific amino acid/auxin permease (AAAP) 1 transporter family. The encoded protein functions as a proton-dependent, small amino acid transporter. This gene is clustered with related family members on chromosome 5q33.1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21825352).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_078483.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC36A1	NM_078483.4	MANE Select	c.421C>G	p.Arg141Gly	missense splice_region	Exon 6 of 11	NP_510968.2
	SLC36A1	NM_001349740.2		c.337C>G	p.Arg113Gly	missense splice_region	Exon 7 of 12	NP_001336669.1
	SLC36A1	NM_001308150.2		c.421C>G	p.Arg141Gly	missense splice_region	Exon 6 of 11	NP_001295079.1	Q7Z2H8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC36A1	ENST00000243389.8	TSL:1 MANE Select	c.421C>G	p.Arg141Gly	missense splice_region	Exon 6 of 11	ENSP00000243389.3	Q7Z2H8-1
	SLC36A1	ENST00000521925.5	TSL:1	c.421C>G	p.Arg141Gly	missense splice_region	Exon 6 of 10	ENSP00000430305.1	E7EW39
	SLC36A1	ENST00000429484.6	TSL:1	c.421C>G	p.Arg141Gly	missense splice_region	Exon 6 of 9	ENSP00000395640.2	Q7Z2H8-4

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 151562 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000205 AC: 51 AN: 248922 AF XY: 0.000230

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.000234

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000230

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000211 AC: 307 AN: 1455992 Hom.: 1 Cov.: 31 AF XY: 0.000239 AC XY: 173 AN XY: 724556

African (AFR) AF: 0.000272 AC: 9 AN: 33130

American (AMR) AF: 0.000249 AC: 11 AN: 44142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.000585 AC: 50 AN: 85510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00400 AC: 23 AN: 5746

European-Non Finnish (NFE) AF: 0.000175 AC: 194 AN: 1108250

Other (OTH) AF: 0.000332 AC: 20 AN: 60162

GnomAD4 genome AF: 0.000125 AC: 19 AN: 151680 Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8 AN XY: 74066

African (AFR) AF: 0.0000484 AC: 2 AN: 41328

American (AMR) AF: 0.0000656 AC: 1 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67956

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.000146 Hom.: 0

Bravo AF: 0.000242

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.000214 AC: 26

EpiCase AF: 0.000655

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.070
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.96	L
PhyloP100		1.7
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.081
Sift	Benign	0.27	T
Sift4G	Benign	0.29	T
Polyphen		0.047	B
Vest4		0.55
MVP		0.39
MPC		0.44
ClinPred		0.022	T
GERP RS		4.2
Varity_R		0.20
gMVP		0.36
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0030
dbscSNV1_RF	Benign	0.054
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

Other links and lift over

dbSNP: rs35204299; hg19: chr5-150846761;