3-196216610-C-T

Variant names:

• chr3-196216610-C-T
• rs56030157
• NM_152672.6:c.-103C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

PCYT1A Gene-Disease associations (from GenCC):

• spondylometaphyseal dysplasia-cone-rod dystrophy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• Leber congenital amaurosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000309772 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152672.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC51A	NM_152672.6	MANE Select	c.-103C>T		5_prime_UTR	Exon 1 of 9	NP_689885.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC51A	ENST00000296327.10	TSL:1 MANE Select	c.-103C>T		5_prime_UTR	Exon 1 of 9	ENSP00000296327.5	Q86UW1
	SLC51A	ENST00000900649.1		c.-103C>T		5_prime_UTR	Exon 1 of 10	ENSP00000570708.1
	SLC51A	ENST00000900648.1		c.-103C>T		5_prime_UTR	Exon 1 of 8	ENSP00000570707.1

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

GnomAD2 exomes AF: 0.231 AC: 31566 AN: 136590 AF XY: 0.233

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 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

African (AFR) AF: 0.0431 AC: 1047 AN: 24278

American (AMR) AF: 0.233 AC: 8144 AN: 34980

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 4247 AN: 22656

East Asian (EAS) AF: 0.431 AC: 14604 AN: 33894

South Asian (SAS) AF: 0.251 AC: 17868 AN: 71114

European-Finnish (FIN) AF: 0.234 AC: 9986 AN: 42648

Middle Eastern (MID) AF: 0.241 AC: 911 AN: 3784

European-Non Finnish (NFE) AF: 0.197 AC: 141215 AN: 718006

Other (OTH) AF: 0.209 AC: 9310 AN: 44520

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

African (AFR) AF: 0.0520 AC: 2158 AN: 41508

American (AMR) AF: 0.225 AC: 3435 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 640 AN: 3470

East Asian (EAS) AF: 0.419 AC: 2151 AN: 5136

South Asian (SAS) AF: 0.259 AC: 1250 AN: 4820

European-Finnish (FIN) AF: 0.225 AC: 2381 AN: 10596

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13542 AN: 67948

Other (OTH) AF: 0.180 AC: 380 AN: 2108

Alfa AF: 0.129 Hom.: 324

Bravo AF: 0.169

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.53
PhyloP100		-0.43
PromoterAI		-0.046	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs56030157; hg19: chr3-195943481;