NM_152672.6:c.134-6_134-4dupCTC

Variant names:

• chr3-196226952-T-TCTC
• rs925691713
• NM_152672.6:c.134-6_134-4dupCTC

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP6

The NM_152672.6(SLC51A):​c.134-6_134-4dupCTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,605,338 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC51A NM_152672.6 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.26
• 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]

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

ENSG00000309772 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 3-196226952-T-TCTC is Benign according to our data. Variant chr3-196226952-T-TCTC is described in ClinVar as [Likely_benign]. Clinvar id is 3029115.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.134-6_134-4dupCTC		splice_region_variant, intron_variant	Intron 2 of 8	ENST00000296327.10	NP_689885.4
SLC51A	XM_047447662.1	c.-215-6_-215-4dupCTC		splice_region_variant, intron_variant	Intron 1 of 7		XP_047303618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC51A	ENST00000296327.10	c.134-13_134-12insCTC		intron_variant	Intron 2 of 8	1	NM_152672.6	ENSP00000296327.5

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152078 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000411 AC: 1 AN: 243338 AF XY: 0.00000760

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000302

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453260 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 722620

African (AFR) AF: 0.00 AC: 0 AN: 33170

American (AMR) AF: 0.0000462 AC: 2 AN: 43286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25318

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 85166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5654

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107982

Other (OTH) AF: 0.00 AC: 0 AN: 59954

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152078 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74284

African (AFR) AF: 0.00 AC: 0 AN: 41408

American (AMR) AF: 0.000197 AC: 3 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SLC51A-related disorder Benign:1

Jan 09, 2024

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
PhyloP100		1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs925691713; hg19: chr3-195953823;