11-63014703-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_004254.4(SLC22A8):c.256A>G(p.Asn86Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC22A8 NM_004254.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.29

Genes affected

SLC22A8 (HGNC:10972): (solute carrier family 22 member 8) This gene encodes a protein involved in the sodium-independent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and appears to be localized to the basolateral membrane of the kidney. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity S22A8_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A8	NM_004254.4	c.256A>G	p.Asn86Asp	missense_variant	2/11	ENST00000336232.7
SLC22A8	NM_001184732.2	c.256A>G	p.Asn86Asp	missense_variant	2/11
SLC22A8	NM_001184733.2	c.-18A>G		5_prime_UTR_variant	2/11
SLC22A8	NM_001184736.2	c.-37+1026A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A8	ENST00000336232.7	c.256A>G	p.Asn86Asp	missense_variant	2/11	1	NM_004254.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

The c.256A>G (p.N86D) alteration is located in exon 2 (coding exon 1) of the SLC22A8 gene. This alteration results from a A to G substitution at nucleotide position 256, causing the asparagine (N) at amino acid position 86 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T;T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.77	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	1.8	L;.;L
MutationTaster	Benign	0.89	D;D;D;D;D
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.2	D;D;D
REVEL	Uncertain	0.53
Sift	Benign	0.062	T;T;T
Sift4G	Uncertain	0.058	T;D;T
Polyphen		0.91	P;.;P
Vest4		0.55
MutPred		0.53		Gain of phosphorylation at T88 (P = 0.1259);Gain of phosphorylation at T88 (P = 0.1259);Gain of phosphorylation at T88 (P = 0.1259);
MVP		0.55
MPC		1.2
ClinPred		0.95	D
GERP RS		4.0
Varity_R		0.15
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-62782175;