3-196226969-G-T

Variant summary

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

The NM_152672.6(SLC51A):c.138G>T(p.Leu46=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000394 in 1,612,774 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: SLC51A NM_152672.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.66

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 3-196226969-G-T is Benign according to our data. Variant chr3-196226969-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3048712.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC51A	NM_152672.6	c.138G>T	p.Leu46=	synonymous_variant	3/9	ENST00000296327.10
SLC51A	XM_047447662.1	c.-211G>T		5_prime_UTR_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC51A	ENST00000296327.10	c.138G>T	p.Leu46=	synonymous_variant	3/9	1	NM_152672.6	P1

Frequencies

GnomAD3 genomes AF: 0.00157 AC: 238 AN: 151996 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00495

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000722

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.000612 AC: 153 AN: 249958 Hom.: 1 AF XY: 0.000489 AC XY: 66 AN XY: 135060

Gnomad AFR exome AF: 0.00480

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000657

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.000493

GnomAD4 exome AF: 0.000270 AC: 395 AN: 1460660 Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 185 AN XY: 726628

Gnomad4 AFR exome AF: 0.00484

Gnomad4 AMR exome AF: 0.00139

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000108

Gnomad4 OTH exome AF: 0.000547

GnomAD4 genome AF: 0.00158 AC: 241 AN: 152114 Hom.: 1 Cov.: 32 AF XY: 0.00164 AC XY: 122 AN XY: 74380

Gnomad4 AFR AF: 0.00506

Gnomad4 AMR AF: 0.000721

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000749 Hom.: 0

Bravo AF: 0.00170

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SLC51A-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 13, 2021

This variant is classified as likely 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	-0.54
Cadd	Benign	5.9
Dann	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs145068718; hg19: chr3-195953840; COSMIC: COSV56352924; COSMIC: COSV56352924;