Genetic Variant SLC51A:c.780+38C>T (chr3-196230099-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152672.6(SLC51A):c.780+38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 1,552,664 control chromosomes in the GnomAD database, including 84,599 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 8127 hom., cov: 32)

Exomes 𝑓: 0.32 ( 76472 hom. )

Consequence

SLC51A
NM_152672.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0810

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC51A	NM_152672.6 link	c.780+38C>T		intron_variant	Intron 7 of 8	ENST00000296327.10	NP_689885.4	Q86UW1
SLC51A	XM_047447662.1 link	c.432+38C>T		intron_variant	Intron 6 of 7		XP_047303618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC51A	ENST00000296327.10 link	c.780+38C>T		intron_variant	Intron 7 of 8	1	NM_152672.6	ENSP00000296327.5		Q86UW1

Frequencies

GnomAD3 genomes

AF:

0.311

AC:

47328

AN:

151974

Hom.:

8109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.233

Gnomad AMR

AF:

0.408

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.749

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.309

Gnomad OTH

AF:

0.318

GnomAD3 exomes

AF:

0.351

AC:

70588

AN:

201074

Hom.:

13842

AF XY:

0.345

AC XY:

37508

AN XY:

108806

show subpopulations

Gnomad AFR exome

AF:

0.244

Gnomad AMR exome

AF:

0.466

Gnomad ASJ exome

AF:

0.276

Gnomad EAS exome

AF:

0.754

Gnomad SAS exome

AF:

0.317

Gnomad FIN exome

AF:

0.243

Gnomad NFE exome

AF:

0.311

Gnomad OTH exome

AF:

0.317

GnomAD4 exome

AF:

0.319

AC:

446881

AN:

1400572

Hom.:

76472

Cov.:

AF XY:

0.318

AC XY:

220580

AN XY:

694088

show subpopulations

Gnomad4 AFR exome

AF:

0.244

Gnomad4 AMR exome

AF:

0.450

Gnomad4 ASJ exome

AF:

0.261

Gnomad4 EAS exome

AF:

0.775

Gnomad4 SAS exome

AF:

0.302

Gnomad4 FIN exome

AF:

0.239

Gnomad4 NFE exome

AF:

0.308

Gnomad4 OTH exome

AF:

0.314

GnomAD4 genome

AF:

0.312

AC:

47384

AN:

152092

Hom.:

8127

Cov.:

AF XY:

0.313

AC XY:

23287

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.249

Gnomad4 AMR

AF:

0.408

Gnomad4 ASJ

AF:

0.261

Gnomad4 EAS

AF:

0.750

Gnomad4 SAS

AF:

0.323

Gnomad4 FIN

AF:

0.235

Gnomad4 NFE

AF:

0.309

Gnomad4 OTH

AF:

0.323

Alfa

AF:

0.219

Hom.:

747

Bravo

AF:

0.327

Asia WGS

AF:

0.492

AC:

1708

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.9

DANN

Benign

0.44

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over