chr3-196229956-T-C

Variant names:

• chr3-196229956-T-C
• rs17852687
• NM_152672.6:c.675T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The ENST00000296327.10(SLC51A):​c.675T>C​(p.Leu225Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 1,612,724 control chromosomes in the GnomAD database, including 173,328 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.44 (15086 hom., cov: 32)
  • Exomes 𝑓: 0.46 (158242 hom.)
• Consequence: SLC51A ENST00000296327.10 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -8.04
• Publications: 18 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 3-196229956-T-C is Benign according to our data. Variant chr3-196229956-T-C is described in ClinVar as Benign. ClinVar VariationId is 3060917.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-8.04 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000296327.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC51A	NM_152672.6	MANE Select	c.675T>C	p.Leu225Leu	synonymous	Exon 7 of 9	NP_689885.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC51A	ENST00000296327.10	TSL:1 MANE Select	c.675T>C	p.Leu225Leu	synonymous	Exon 7 of 9	ENSP00000296327.5
	SLC51A	ENST00000475672.5	TSL:1	n.527T>C		non_coding_transcript_exon	Exon 4 of 5
	SLC51A	ENST00000484407.5	TSL:1	n.487T>C		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66282 AN: 151932 Hom.: 15074 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.437

GnomAD2 exomes AF: 0.483 AC: 120527 AN: 249796 AF XY: 0.480

Gnomad AFR exome AF: 0.346

Gnomad AMR exome AF: 0.549

Gnomad ASJ exome AF: 0.407

Gnomad EAS exome AF: 0.818

Gnomad FIN exome AF: 0.411

Gnomad NFE exome AF: 0.451

Gnomad OTH exome AF: 0.448

GnomAD4 exome AF: 0.460 AC: 671722 AN: 1460674 Hom.: 158242 Cov.: 50 AF XY: 0.460 AC XY: 334046 AN XY: 726704

African (AFR) AF: 0.349 AC: 11645 AN: 33402

American (AMR) AF: 0.541 AC: 24109 AN: 44560

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 10524 AN: 26094

East Asian (EAS) AF: 0.819 AC: 32435 AN: 39580

South Asian (SAS) AF: 0.472 AC: 40620 AN: 86114

European-Finnish (FIN) AF: 0.409 AC: 21819 AN: 53376

Middle Eastern (MID) AF: 0.400 AC: 2305 AN: 5760

European-Non Finnish (NFE) AF: 0.451 AC: 500989 AN: 1111434

Other (OTH) AF: 0.452 AC: 27276 AN: 60354

GnomAD4 genome AF: 0.436 AC: 66329 AN: 152050 Hom.: 15086 Cov.: 32 AF XY: 0.439 AC XY: 32590 AN XY: 74308

African (AFR) AF: 0.352 AC: 14610 AN: 41478

American (AMR) AF: 0.499 AC: 7629 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1395 AN: 3470

East Asian (EAS) AF: 0.806 AC: 4166 AN: 5166

South Asian (SAS) AF: 0.483 AC: 2327 AN: 4818

European-Finnish (FIN) AF: 0.409 AC: 4319 AN: 10566

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30480 AN: 67952

Other (OTH) AF: 0.440 AC: 931 AN: 2116

Alfa AF: 0.432 Hom.: 9045

Bravo AF: 0.444

Asia WGS AF: 0.609 AC: 2114 AN: 3478

EpiCase AF: 0.443

EpiControl AF: 0.448

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.98
CADD	Benign	0.034
DANN	Benign	0.39
PhyloP100		-8.0
PromoterAI		0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs17852687; hg19: chr3-195956827; COSMIC: COSV53056425; COSMIC: COSV53056425;