5-102388783-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_173488.5(SLCO6A1):c.1922C>G(p.Thr641Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLCO6A1 NM_173488.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.80

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046913177).
• BP6: Variant 5-102388783-G-C is Benign according to our data. Variant chr5-102388783-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2233895.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO6A1	NM_173488.5	c.1922C>G	p.Thr641Ser	missense_variant	12/14	ENST00000506729.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO6A1	ENST00000506729.6	c.1922C>G	p.Thr641Ser	missense_variant	12/14	1	NM_173488.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	0.0010
Dann	Benign	0.044
DEOGEN2	Benign	0.032	T;T;.;.
Eigen	Benign	-2.8
Eigen_PC	Benign	-2.8
FATHMM_MKL	Benign	0.0051	N
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.047	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.67	N;N;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.13	N;N;N;N
REVEL	Benign	0.068
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	0.60	T;T;T;T
Polyphen		0.0010	B;B;B;B
Vest4		0.049
MutPred		0.41		Gain of disorder (P = 0.0312);Gain of disorder (P = 0.0312);.;.;
MVP		0.15
MPC		0.096
ClinPred		0.042	T
GERP RS		-10
Varity_R		0.028
gMVP		0.094

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs370646896; hg19: chr5-101724487;