3-196233354-A-G

Variant names:

• chr3-196233354-A-G
• rs9343
• ENST00000484407.5:n.990A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000484407.5(SLC51A):​n.990A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 831,946 control chromosomes in the GnomAD database, including 108,085 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 0.50 (19609 hom., cov: 33)
  • Exomes 𝑓: 0.50 (88476 hom.)
• Consequence: SLC51A ENST00000484407.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.112
• Publications: 14 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: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
• Leber congenital amaurosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC51A	NM_152672.6	c.*155A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000296327.10	NP_689885.4
SLC51A	XM_047447662.1	c.*155A>G		3_prime_UTR_variant	Exon 8 of 8		XP_047303618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC51A	ENST00000296327.10	c.*155A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_152672.6	ENSP00000296327.5

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76102 AN: 152052 Hom.: 19578 Cov.: 33

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.487

GnomAD4 exome AF: 0.499 AC: 339050 AN: 679776 Hom.: 88476 Cov.: 9 AF XY: 0.499 AC XY: 174355 AN XY: 349352

African (AFR) AF: 0.506 AC: 8410 AN: 16626

American (AMR) AF: 0.550 AC: 11616 AN: 21128

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 6385 AN: 15228

East Asian (EAS) AF: 0.883 AC: 29256 AN: 33132

South Asian (SAS) AF: 0.539 AC: 27626 AN: 51264

European-Finnish (FIN) AF: 0.430 AC: 14344 AN: 33370

Middle Eastern (MID) AF: 0.442 AC: 1714 AN: 3876

European-Non Finnish (NFE) AF: 0.473 AC: 223202 AN: 471512

Other (OTH) AF: 0.490 AC: 16497 AN: 33640

GnomAD4 genome AF: 0.501 AC: 76181 AN: 152170 Hom.: 19609 Cov.: 33 AF XY: 0.503 AC XY: 37433 AN XY: 74408

African (AFR) AF: 0.506 AC: 20989 AN: 41502

American (AMR) AF: 0.535 AC: 8185 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1455 AN: 3472

East Asian (EAS) AF: 0.885 AC: 4590 AN: 5184

South Asian (SAS) AF: 0.552 AC: 2662 AN: 4826

European-Finnish (FIN) AF: 0.424 AC: 4489 AN: 10588

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32281 AN: 67988

Other (OTH) AF: 0.489 AC: 1032 AN: 2110

Alfa AF: 0.466 Hom.: 6831

Bravo AF: 0.512

Asia WGS AF: 0.686 AC: 2383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.61
PhyloP100		-0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	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: rs9343; hg19: chr3-195960225; COSMIC: COSV53057145; COSMIC: COSV53057145;