rs939885

chr3-196228891-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152672.6(SLC51A):c.604G>A(p.Val202Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 1,613,134 control chromosomes in the GnomAD database, including 188,626 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.43 (15257 hom., cov: 32)
  • Exomes 𝑓: 0.48 (173369 hom.)
• Consequence: SLC51A NM_152672.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0890

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1412093E-6).
• BP6: Variant 3-196228891-G-A is Benign according to our data. Variant chr3-196228891-G-A is described in ClinVar as [Benign]. Clinvar id is 3059296.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC51A	NM_152672.6	c.604G>A	p.Val202Ile	missense_variant	6/9	ENST00000296327.10
SLC51A	XM_047447662.1	c.256G>A	p.Val86Ile	missense_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC51A	ENST00000296327.10	c.604G>A	p.Val202Ile	missense_variant	6/9	1	NM_152672.6	P1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65047 AN: 151850 Hom.: 15243 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.460

GnomAD3 exomes AF: 0.488 AC: 122599 AN: 251448 Hom.: 31592 AF XY: 0.484 AC XY: 65839 AN XY: 135904

Gnomad AFR exome AF: 0.232

Gnomad AMR exome AF: 0.576

Gnomad ASJ exome AF: 0.498

Gnomad EAS exome AF: 0.764

Gnomad SAS exome AF: 0.409

Gnomad FIN exome AF: 0.437

Gnomad NFE exome AF: 0.483

Gnomad OTH exome AF: 0.485

GnomAD4 exome AF: 0.482 AC: 703960 AN: 1461166 Hom.: 173369 Cov.: 42 AF XY: 0.480 AC XY: 348732 AN XY: 726908

Gnomad4 AFR exome AF: 0.236

Gnomad4 AMR exome AF: 0.569

Gnomad4 ASJ exome AF: 0.492

Gnomad4 EAS exome AF: 0.779

Gnomad4 SAS exome AF: 0.407

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.484

Gnomad4 OTH exome AF: 0.472

GnomAD4 genome AF: 0.428 AC: 65092 AN: 151968 Hom.: 15257 Cov.: 32 AF XY: 0.434 AC XY: 32209 AN XY: 74294

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.464

Alfa AF: 0.484 Hom.: 28795

Bravo AF: 0.433

TwinsUK AF: 0.491 AC: 1819

ALSPAC AF: 0.497 AC: 1917

ESP6500AA AF: 0.247 AC: 1089

ESP6500EA AF: 0.478 AC: 4108

ExAC AF: 0.477 AC: 57910

Asia WGS AF: 0.548 AC: 1904 AN: 3478

EpiCase AF: 0.492

EpiControl AF: 0.492

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SLC51A-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 22, 2023

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
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
Cadd	Benign	7.8
Dann	Benign	0.84
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.022	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-2.0	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.047
Sift	Benign	0.95	T
Sift4G	Benign	0.82	T
Polyphen		0.0	B
Vest4		0.029
MPC		0.11
ClinPred		0.0042	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.019
gMVP		0.43

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

Other links and lift over

dbSNP: rs939885; hg19: chr3-195955762; COSMIC: COSV56351677; COSMIC: COSV56351677;