Genetic Variant SLC51A:p.Leu225Leu (chr3-196229956-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_152672.6(SLC51A):c.675T>C(p.Leu225Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 1,612,724 control chromosomes in the GnomAD database, including 173,328 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.44 ( 15086 hom., cov: 32)

Exomes 𝑓: 0.46 ( 158242 hom. )

Consequence

SLC51A
NM_152672.6 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -8.04

Variant links:

Genes affected

SLC51A (HGNC:29955): (solute carrier family 51 member A) Predicted to enable protein heterodimerization activity; protein homodimerization activity; and transmembrane transporter activity. Involved in bile acid secretion. Located in basolateral plasma membrane. Implicated in progressive familial intrahepatic cholestasis. [provided by Alliance of Genome Resources, Apr 2022]

SLC51A links:

PCYT1A (HGNC:8754): (phosphate cytidylyltransferase 1A, choline) This gene belongs to the cytidylyltransferase family and is involved in the regulation of phosphatidylcholine biosynthesis. Mutations in this gene are associated with spondylometaphyseal dysplasia with cone-rod dystrophy. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2015]

PCYT1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 3-196229956-T-C is Benign according to our data. Variant chr3-196229956-T-C is described in ClinVar as [Benign]. Clinvar id is 3060917.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-8.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC51A	NM_152672.6 link	c.675T>C	p.Leu225Leu	synonymous_variant	Exon 7 of 9	ENST00000296327.10	NP_689885.4	Q86UW1
SLC51A	XM_047447662.1 link	c.327T>C	p.Leu109Leu	synonymous_variant	Exon 6 of 8		XP_047303618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC51A	ENST00000296327.10 link	c.675T>C	p.Leu225Leu	synonymous_variant	Exon 7 of 9	1	NM_152672.6	ENSP00000296327.5		Q86UW1

Frequencies

GnomAD3 genomes

AF:

0.436

AC:

66282

AN:

151932

Hom.:

15074

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.499

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.806

Gnomad SAS

AF:

0.484

Gnomad FIN

AF:

0.409

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.449

Gnomad OTH

AF:

0.437

GnomAD3 exomes

AF:

0.483

AC:

120527

AN:

249796

Hom.:

30584

AF XY:

0.480

AC XY:

64819

AN XY:

135118

show subpopulations

Gnomad AFR exome

AF:

0.346

Gnomad AMR exome

AF:

0.549

Gnomad ASJ exome

AF:

0.407

Gnomad EAS exome

AF:

0.818

Gnomad SAS exome

AF:

0.477

Gnomad FIN exome

AF:

0.411

Gnomad NFE exome

AF:

0.451

Gnomad OTH exome

AF:

0.448

GnomAD4 exome

AF:

0.460

AC:

671722

AN:

1460674

Hom.:

158242

Cov.:

AF XY:

0.460

AC XY:

334046

AN XY:

726704

show subpopulations

Gnomad4 AFR exome

AF:

0.349

Gnomad4 AMR exome

AF:

0.541

Gnomad4 ASJ exome

AF:

0.403

Gnomad4 EAS exome

AF:

0.819

Gnomad4 SAS exome

AF:

0.472

Gnomad4 FIN exome

AF:

0.409

Gnomad4 NFE exome

AF:

0.451

Gnomad4 OTH exome

AF:

0.452

GnomAD4 genome

AF:

0.436

AC:

66329

AN:

152050

Hom.:

15086

Cov.:

AF XY:

0.439

AC XY:

32590

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.352

Gnomad4 AMR

AF:

0.499

Gnomad4 ASJ

AF:

0.402

Gnomad4 EAS

AF:

0.806

Gnomad4 SAS

AF:

0.483

Gnomad4 FIN

AF:

0.409

Gnomad4 NFE

AF:

0.449

Gnomad4 OTH

AF:

0.440

Alfa

AF:

0.428

Hom.:

6883

Bravo

AF:

0.444

Asia WGS

AF:

0.609

AC:

2114

AN:

3478

EpiCase

AF:

0.443

EpiControl

AF:

0.448

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SLC51A-related disorder

Benign:1

Jun 22, 2023

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.034

DANN

Benign

0.39

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over