NM_001384763.1:c.1042G>A

Variant names:

• chr16-89196298-C-T
• rs1389937169
• NM_001384763.1:c.1042G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001384763.1(SLC22A31):​c.1042G>A​(p.Gly348Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,351,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: SLC22A31 NM_001384763.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.343
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28902316).

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.1042G>A	p.Gly348Arg	missense	Exon 9 of 9	NP_001371692.1	A6NKX4-2
	SLC22A31	NM_001366322.1		c.988G>A	p.Gly330Arg	missense	Exon 9 of 9	NP_001353251.1
	SLC22A31	NM_001384764.1		c.841G>A	p.Gly281Arg	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.1042G>A	p.Gly348Arg	missense	Exon 9 of 9	ENSP00000508250.1	A6NKX4-2
	SLC22A31	ENST00000562855.7	TSL:5	c.718G>A	p.Gly240Arg	missense	Exon 9 of 9	ENSP00000474621.2	A0A087WY01
	SLC22A31	ENST00000614943.4	TSL:5	c.718G>A	p.Gly240Arg	missense	Exon 8 of 8	ENSP00000481421.1	A0A087WY01

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000148 AC: 2 AN: 1351718 Hom.: 0 Cov.: 31 AF XY: 0.00000150 AC XY: 1 AN XY: 665292

African (AFR) AF: 0.00 AC: 0 AN: 30678

American (AMR) AF: 0.00 AC: 0 AN: 32596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22998

East Asian (EAS) AF: 0.0000285 AC: 1 AN: 35058

South Asian (SAS) AF: 0.00 AC: 0 AN: 74520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3952

European-Non Finnish (NFE) AF: 9.40e-7 AC: 1 AN: 1063494

Other (OTH) AF: 0.00 AC: 0 AN: 56382

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	18
DANN	Benign	0.86
DEOGEN2	Benign	0.22	T
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.29	T
PhyloP100		0.34
PrimateAI	Uncertain	0.68	T
Sift4G	Benign	0.19	T
Vest4		0.44
MVP		0.57
GERP RS		2.2
Varity_R		0.064
Mutation Taster		=94/6	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: rs1389937169; hg19: chr16-89262706;