16-89196015-G-T

Variant names:

• chr16-89196015-G-T
• rs780900997
• NM_001384763.1:c.1325C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001384763.1(SLC22A31):​c.1325C>A​(p.Thr442Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,514,060 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: SLC22A31 NM_001384763.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.810
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0061670244).

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.1325C>A	p.Thr442Asn	missense	Exon 9 of 9	NP_001371692.1	A6NKX4-2
	SLC22A31	NM_001366322.1		c.1271C>A	p.Thr424Asn	missense	Exon 9 of 9	NP_001353251.1
	SLC22A31	NM_001384764.1		c.1124C>A	p.Thr375Asn	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.1325C>A	p.Thr442Asn	missense	Exon 9 of 9	ENSP00000508250.1	A6NKX4-2
	SLC22A31	ENST00000562855.7	TSL:5	c.1001C>A	p.Thr334Asn	missense	Exon 9 of 9	ENSP00000474621.2	A0A087WY01
	SLC22A31	ENST00000614943.4	TSL:5	c.1001C>A	p.Thr334Asn	missense	Exon 8 of 8	ENSP00000481421.1	A0A087WY01

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000268 AC: 32 AN: 119278 AF XY: 0.000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000152

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000238

Gnomad OTH exome AF: 0.00108

GnomAD4 exome AF: 0.000156 AC: 213 AN: 1361734 Hom.: 1 Cov.: 30 AF XY: 0.000175 AC XY: 117 AN XY: 669534

African (AFR) AF: 0.00 AC: 0 AN: 31112

American (AMR) AF: 0.00 AC: 0 AN: 34060

Ashkenazi Jewish (ASJ) AF: 0.0000847 AC: 2 AN: 23616

East Asian (EAS) AF: 0.00 AC: 0 AN: 35460

South Asian (SAS) AF: 0.000659 AC: 50 AN: 75886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32690

Middle Eastern (MID) AF: 0.00222 AC: 9 AN: 4060

European-Non Finnish (NFE) AF: 0.000118 AC: 126 AN: 1068078

Other (OTH) AF: 0.000458 AC: 26 AN: 56772

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152326 Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13 AN XY: 74486

African (AFR) AF: 0.0000481 AC: 2 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68018

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000565 Hom.: 0

Bravo AF: 0.000128

ExAC AF: 0.000474 AC: 10

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	0.091
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.54
DANN	Benign	0.61
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.0062	T
PhyloP100		-0.81
PrimateAI	Benign	0.42	T
Sift4G	Pathogenic	0.0	D
Vest4		0.069
MVP		0.20
GERP RS		1.3
Varity_R		0.023
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: rs780900997; hg19: chr16-89262423;