3-196229956-T-C

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: š‘“ 0.44 ( 15086 hom., cov: 32)
Exomes š‘“: 0.46 ( 158242 hom. )

Consequence

SLC51A
NM_152672.6 synonymous

Scores

2

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]
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]

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
SLC51ANM_152672.6 linkc.675T>C p.Leu225Leu synonymous_variant Exon 7 of 9 ENST00000296327.10 NP_689885.4 Q86UW1
SLC51AXM_047447662.1 linkc.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
SLC51AENST00000296327.10 linkc.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.:
32
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.:
50
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.:
32
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.

Other links and lift over

dbSNP: rs17852687; hg19: chr3-195956827; COSMIC: COSV53056425; COSMIC: COSV53056425; API