5-151467783-C-T

Variant names:

• chr5-151467783-C-T
• rs571362914
• NM_078483.4:c.581C>T

Variant summary

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

The NM_078483.4(SLC36A1):​c.581C>T​(p.Ser194Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: SLC36A1 NM_078483.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.70
• Publications: 0 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=0.1596545).

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.581C>T	p.Ser194Leu	missense	Exon 7 of 11	NP_510968.2
	SLC36A1	NM_001349740.2		c.497C>T	p.Ser166Leu	missense	Exon 8 of 12	NP_001336669.1
	SLC36A1	NM_001308150.2		c.581C>T	p.Ser194Leu	missense	Exon 7 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.581C>T	p.Ser194Leu	missense	Exon 7 of 11	ENSP00000243389.3	Q7Z2H8-1
	SLC36A1	ENST00000521925.5	TSL:1	c.581C>T	p.Ser194Leu	missense	Exon 7 of 10	ENSP00000430305.1	E7EW39
	SLC36A1	ENST00000429484.6	TSL:1	c.581C>T	p.Ser194Leu	missense	Exon 7 of 9	ENSP00000395640.2	Q7Z2H8-4

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 152052 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000775

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000676 AC: 17 AN: 251488 AF XY: 0.0000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000924

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1461868 Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 15 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000378 AC: 15 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152170 Hom.: 0 Cov.: 30 AF XY: 0.0000672 AC XY: 5 AN XY: 74404

African (AFR) AF: 0.00 AC: 0 AN: 41518

American (AMR) AF: 0.0000654 AC: 1 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000777 AC: 4 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000659 AC: 8

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	-0.23	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.082
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.7
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.25
Sift	Benign	0.59	T
Sift4G	Benign	0.35	T
Polyphen		0.46	P
Vest4		0.83
MutPred		0.54		Loss of catalytic residue at S194 (P = 0.096)
MVP		0.32
MPC		0.37
ClinPred		0.099	T
GERP RS		4.8
Varity_R		0.17
gMVP		0.80
Mutation Taster		=38/62	disease causing

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

Other links and lift over

dbSNP: rs571362914; hg19: chr5-150847344;