chr3-196216707-G-A

Variant names:

• chr3-196216707-G-A
• rs747550066
• NM_152672.6:c.-6G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP6

The NM_152672.6(SLC51A):​c.-6G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000268 in 1,567,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: SLC51A NM_152672.6 5_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.679
• Publications: 0 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]

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]

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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08129436).
• BP6: Variant 3-196216707-G-A is Benign according to our data. Variant chr3-196216707-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3052279.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC51A	NM_152672.6	c.-6G>A		5_prime_UTR_variant	Exon 1 of 9	ENST00000296327.10	NP_689885.4

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 151950 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000284 AC: 5 AN: 176256 AF XY: 0.0000210

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000356

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000570

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000275 AC: 39 AN: 1415834 Hom.: 0 Cov.: 33 AF XY: 0.0000314 AC XY: 22 AN XY: 700264

African (AFR) AF: 0.00 AC: 0 AN: 32352

American (AMR) AF: 0.0000257 AC: 1 AN: 38952

Ashkenazi Jewish (ASJ) AF: 0.0000394 AC: 1 AN: 25396

East Asian (EAS) AF: 0.0000269 AC: 1 AN: 37166

South Asian (SAS) AF: 0.00 AC: 0 AN: 80680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48652

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.0000322 AC: 35 AN: 1088404

Other (OTH) AF: 0.0000171 AC: 1 AN: 58532

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151950 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74222

African (AFR) AF: 0.00 AC: 0 AN: 41312

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000340

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SLC51A-related disorder Benign:1

Jan 11, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.6
DANN	Benign	0.89
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.68
PROVEAN	Benign	0.0	N
REVEL	Benign	0.066
MutPred		0.12		Gain of glycosylation at A43 (P = 0.0564);
MVP		0.076
ClinPred		0.031	T
GERP RS		-1.7
PromoterAI		0.030	Neutral
Mutation Taster		=98/2	polymorphism

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: rs747550066; hg19: chr3-195943578;