12-16189714-A-C

Variant names:

• chr12-16189714-A-C
• NM_001170798.1:c.1694T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001170798.1(SLC15A5):​c.1694T>G​(p.Ile565Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,378,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: SLC15A5 NM_001170798.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03
• Publications: 0 publications found

Genes affected

SLC15A5 (HGNC:33455): (solute carrier family 15 member 5) Predicted to enable symporter activity. Predicted to be involved in peptide transport; protein transport; and transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC101928362 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.073168784).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170798.1. 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
	SLC15A5	NM_001170798.1	MANE Select	c.1694T>G	p.Ile565Arg	missense	Exon 9 of 9	NP_001164269.1	A6NIM6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC15A5	ENST00000344941.3	TSL:5 MANE Select	c.1694T>G	p.Ile565Arg	missense	Exon 9 of 9	ENSP00000340402.3	A6NIM6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1378728 Hom.: 0 Cov.: 30 AF XY: 0.00000294 AC XY: 2 AN XY: 680076

African (AFR) AF: 0.00 AC: 0 AN: 31304

American (AMR) AF: 0.00 AC: 0 AN: 34940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24920

East Asian (EAS) AF: 0.00 AC: 0 AN: 35640

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34754

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5654

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076108

Other (OTH) AF: 0.0000173 AC: 1 AN: 57670

GnomAD4 genome Cov.: 33

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	0.081
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.0
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.048
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.024	D
Vest4		0.16
MutPred		0.39		Gain of disorder (P = 0.0133)
MVP		0.15
ClinPred		0.17	T
GERP RS		-0.33
Varity_R		0.12
gMVP		0.77
Mutation Taster		=95/5	polymorphism

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

hg19: chr12-16342648;