16-89196022-C-T

Variant names:

• chr16-89196022-C-T
• rs1597316476
• NM_001384763.1:c.1318G>A

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.1318G>A​(p.Gly440Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000022 in 1,366,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/12 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: 0.0000022 (0 hom.)
• Consequence: SLC22A31 NM_001384763.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.894
• Publications: 0 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=0.08001363).

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.1318G>A	p.Gly440Ser	missense	Exon 9 of 9	NP_001371692.1	A6NKX4-2
	SLC22A31	NM_001366322.1		c.1264G>A	p.Gly422Ser	missense	Exon 9 of 9	NP_001353251.1
	SLC22A31	NM_001384764.1		c.1117G>A	p.Gly373Ser	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.1318G>A	p.Gly440Ser	missense	Exon 9 of 9	ENSP00000508250.1	A6NKX4-2
	SLC22A31	ENST00000562855.7	TSL:5	c.994G>A	p.Gly332Ser	missense	Exon 9 of 9	ENSP00000474621.2	A0A087WY01
	SLC22A31	ENST00000614943.4	TSL:5	c.994G>A	p.Gly332Ser	missense	Exon 8 of 8	ENSP00000481421.1	A0A087WY01

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000220 AC: 3 AN: 1366258 Hom.: 0 Cov.: 30 AF XY: 0.00000149 AC XY: 1 AN XY: 672220

African (AFR) AF: 0.00 AC: 0 AN: 31164

American (AMR) AF: 0.00 AC: 0 AN: 34524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23972

East Asian (EAS) AF: 0.0000282 AC: 1 AN: 35498

South Asian (SAS) AF: 0.00 AC: 0 AN: 76672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4100

European-Non Finnish (NFE) AF: 9.34e-7 AC: 1 AN: 1070372

Other (OTH) AF: 0.0000175 AC: 1 AN: 56998

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	0.085
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Benign	0.69
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.080	T
PhyloP100		-0.89
PrimateAI	Benign	0.32	T
Sift4G	Pathogenic	0.0	D
Vest4		0.12
MVP		0.20
GERP RS		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.059
Mutation Taster		=99/1	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

dbSNP: rs1597316476; hg19: chr16-89262430;