chr3-196226969-G-T

Variant names:

• chr3-196226969-G-T
• rs145068718
• NM_152672.6:c.138G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4 BP6

The NM_152672.6(SLC51A):​c.138G>T​(p.Leu46Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.000394 in 1,612,774 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. L46L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: SLC51A NM_152672.6 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.66
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.221).
• BP6: Variant 3-196226969-G-T is Benign according to our data. Variant chr3-196226969-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3048712.Status of the report is no_assertion_criteria_provided, 0 stars.

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.138G>T	p.Leu46Leu	synonymous	Exon 3 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.138G>T	p.Leu46Leu	synonymous	Exon 3 of 9	ENSP00000296327.5	Q86UW1
	SLC51A	ENST00000900647.1		c.138G>T	p.Leu46Leu	synonymous	Exon 4 of 10	ENSP00000570706.1
	SLC51A	ENST00000900649.1		c.138G>T	p.Leu46Leu	synonymous	Exon 3 of 10	ENSP00000570708.1

Frequencies

GnomAD3 genomes AF: 0.00157 AC: 238 AN: 151996 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00495

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000722

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.000612 AC: 153 AN: 249958 AF XY: 0.000489

Gnomad AFR exome AF: 0.00480

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.000493

GnomAD4 exome AF: 0.000270 AC: 395 AN: 1460660 Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 185 AN XY: 726628

African (AFR) AF: 0.00484 AC: 162 AN: 33472

American (AMR) AF: 0.00139 AC: 62 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25982

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

Middle Eastern (MID) AF: 0.00261 AC: 15 AN: 5758

European-Non Finnish (NFE) AF: 0.000108 AC: 120 AN: 1111310

Other (OTH) AF: 0.000547 AC: 33 AN: 60334

GnomAD4 genome AF: 0.00158 AC: 241 AN: 152114 Hom.: 1 Cov.: 32 AF XY: 0.00164 AC XY: 122 AN XY: 74380

African (AFR) AF: 0.00506 AC: 210 AN: 41498

American (AMR) AF: 0.000721 AC: 11 AN: 15254

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67992

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.000749 Hom.: 0

Bravo AF: 0.00170

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SLC51A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.9
DANN	Benign	0.79
PhyloP100		4.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs145068718; hg19: chr3-195953840; COSMIC: COSV56352924; COSMIC: COSV56352924;