5-102459665-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173488.5(SLCO6A1):c.1012A>G(p.Asn338Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000028 in 1,429,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: SLCO6A1 NM_173488.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.811

Genes affected

SLCO6A1 (HGNC:23613): (solute carrier organic anion transporter family member 6A1) Predicted to enable sodium-independent organic anion transmembrane transporter activity. Predicted to be involved in sodium-independent organic anion transport. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24485421).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO6A1	NM_173488.5	c.1012A>G	p.Asn338Asp	missense_variant	5/14	ENST00000506729.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO6A1	ENST00000506729.6	c.1012A>G	p.Asn338Asp	missense_variant	5/14	1	NM_173488.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000280 AC: 4 AN: 1429594 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 710884

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000272

Gnomad4 OTH exome AF: 0.0000170

GnomAD4 genome Cov.: 32

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

Dec 20, 2021

The c.1012A>G (p.N338D) alteration is located in exon 5 (coding exon 5) of the SLCO6A1 gene. This alteration results from a A to G substitution at nucleotide position 1012, causing the asparagine (N) at amino acid position 338 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	0.084
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	1.3
Dann	Benign	0.93
DEOGEN2	Benign	0.082	T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.013	N
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.6	L;L;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.28
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.25	T;T;T
Polyphen		0.93	P;P;D
Vest4		0.19
MutPred		0.40		Loss of MoRF binding (P = 0.0845);Loss of MoRF binding (P = 0.0845);.;
MVP		0.37
MPC		0.14
ClinPred		0.85	D
GERP RS		-8.9
Varity_R		0.10
gMVP		0.034

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-101795369;