16-89196097-G-C

Variant names:

• chr16-89196097-G-C
• rs1270235702
• NM_001384763.1:c.1243C>G

Variant summary

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

The NM_001384763.1(SLC22A31):​c.1243C>G​(p.Arg415Gly) 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 1,381,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/12 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. R415C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC22A31 NM_001384763.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.812
• Publications: 1 publications found

Genes affected

SLC22A31 (HGNC:27091): (solute carrier family 22 member 31) Predicted to enable transmembrane transporter activity. Predicted to be involved in ion transport and transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.19665769).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384763.1. 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
	SLC22A31	NM_001384763.1	MANE Select	c.1243C>G	p.Arg415Gly	missense	Exon 9 of 9	NP_001371692.1	A6NKX4-2
	SLC22A31	NM_001366322.1		c.1189C>G	p.Arg397Gly	missense	Exon 9 of 9	NP_001353251.1
	SLC22A31	NM_001384764.1		c.1042C>G	p.Arg348Gly	missense	Exon 9 of 9	NP_001371693.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A31	ENST00000682282.1	MANE Select	c.1243C>G	p.Arg415Gly	missense	Exon 9 of 9	ENSP00000508250.1	A6NKX4-2
	SLC22A31	ENST00000562855.7	TSL:5	c.919C>G	p.Arg307Gly	missense	Exon 9 of 9	ENSP00000474621.2	A0A087WY01
	SLC22A31	ENST00000614943.4	TSL:5	c.919C>G	p.Arg307Gly	missense	Exon 8 of 8	ENSP00000481421.1	A0A087WY01

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000750 AC: 1 AN: 133380 AF XY: 0.0000138

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000193

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1381420 Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 681580

African (AFR) AF: 0.00 AC: 0 AN: 31518

American (AMR) AF: 0.00 AC: 0 AN: 35652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25124

East Asian (EAS) AF: 0.00 AC: 0 AN: 35710

South Asian (SAS) AF: 0.00 AC: 0 AN: 79110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4692

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078280

Other (OTH) AF: 0.0000173 AC: 1 AN: 57726

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	0.0047	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	15
DANN	Benign	0.65
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.54	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.20	T
PhyloP100		0.81
PrimateAI	Uncertain	0.63	T
Sift4G	Uncertain	0.0070	D
Vest4		0.23
MVP		0.55
GERP RS		-0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.11

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: rs1270235702; hg19: chr16-89262505;