chr3-196216610-C-T

Position:

• chr3-196216610-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152672.6(SLC51A):​c.-103C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,147,956 control chromosomes in the GnomAD database, including 30,119 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 0.17 (2884 hom., cov: 32)
  • Exomes 𝑓: 0.21 (27235 hom.)
• Consequence: SLC51A NM_152672.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435

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]

LOC105374304 (HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC51A	NM_152672.6	c.-103C>T		5_prime_UTR_variant	1/9	ENST00000296327.10	NP_689885.4
LOC105374304	XR_001740544.2	n.1130+2054G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC51A	ENST00000296327.10	c.-103C>T		5_prime_UTR_variant	1/9	1	NM_152672.6	ENSP00000296327	P1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26184 AN: 151962 Hom.: 2892 Cov.: 32

Gnomad AFR AF: 0.0520

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.179

GnomAD3 exomes AF: 0.231 AC: 31566 AN: 136590 Hom.: 3969 AF XY: 0.233 AC XY: 17359 AN XY: 74484

Gnomad AFR exome AF: 0.0468

Gnomad AMR exome AF: 0.238

Gnomad ASJ exome AF: 0.192

Gnomad EAS exome AF: 0.408

Gnomad SAS exome AF: 0.254

Gnomad FIN exome AF: 0.241

Gnomad NFE exome AF: 0.209

Gnomad OTH exome AF: 0.219

GnomAD4 exome AF: 0.208 AC: 207332 AN: 995880 Hom.: 27235 Cov.: 13 AF XY: 0.210 AC XY: 106672 AN XY: 507276

Gnomad4 AFR exome AF: 0.0431

Gnomad4 AMR exome AF: 0.233

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.431

Gnomad4 SAS exome AF: 0.251

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.209

GnomAD4 genome AF: 0.172 AC: 26181 AN: 152076 Hom.: 2884 Cov.: 32 AF XY: 0.176 AC XY: 13109 AN XY: 74320

Gnomad4 AFR AF: 0.0520

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.180

Alfa AF: 0.129 Hom.: 324

Bravo AF: 0.169

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.53

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: rs56030157; hg19: chr3-195943481;