3-196230099-C-T

Variant names:

• chr3-196230099-C-T
• rs67261052
• NM_152672.6:c.780+38C>T

Variant summary

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

The NM_152672.6(SLC51A):​c.780+38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 1,552,664 control chromosomes in the GnomAD database, including 84,599 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 0.31 (8127 hom., cov: 32)
  • Exomes 𝑓: 0.32 (76472 hom.)
• Consequence: SLC51A NM_152672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810
• Publications: 7 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

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.780+38C>T		intron	N/A	NP_689885.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC51A	ENST00000296327.10	TSL:1 MANE Select	c.780+38C>T		intron	N/A	ENSP00000296327.5	Q86UW1
	SLC51A	ENST00000475672.5	TSL:1	n.632+38C>T		intron	N/A
	SLC51A	ENST00000484407.5	TSL:1	n.592+38C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47328 AN: 151974 Hom.: 8109 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.318

GnomAD2 exomes AF: 0.351 AC: 70588 AN: 201074 AF XY: 0.345

Gnomad AFR exome AF: 0.244

Gnomad AMR exome AF: 0.466

Gnomad ASJ exome AF: 0.276

Gnomad EAS exome AF: 0.754

Gnomad FIN exome AF: 0.243

Gnomad NFE exome AF: 0.311

Gnomad OTH exome AF: 0.317

GnomAD4 exome AF: 0.319 AC: 446881 AN: 1400572 Hom.: 76472 Cov.: 33 AF XY: 0.318 AC XY: 220580 AN XY: 694088

African (AFR) AF: 0.244 AC: 7613 AN: 31254

American (AMR) AF: 0.450 AC: 16437 AN: 36558

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 6139 AN: 23522

East Asian (EAS) AF: 0.775 AC: 28536 AN: 36816

South Asian (SAS) AF: 0.302 AC: 23457 AN: 77682

European-Finnish (FIN) AF: 0.239 AC: 12313 AN: 51412

Middle Eastern (MID) AF: 0.267 AC: 1472 AN: 5514

European-Non Finnish (NFE) AF: 0.308 AC: 332774 AN: 1080050

Other (OTH) AF: 0.314 AC: 18140 AN: 57764

GnomAD4 genome AF: 0.312 AC: 47384 AN: 152092 Hom.: 8127 Cov.: 32 AF XY: 0.313 AC XY: 23287 AN XY: 74346

African (AFR) AF: 0.249 AC: 10342 AN: 41482

American (AMR) AF: 0.408 AC: 6231 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 906 AN: 3470

East Asian (EAS) AF: 0.750 AC: 3884 AN: 5180

South Asian (SAS) AF: 0.323 AC: 1556 AN: 4822

European-Finnish (FIN) AF: 0.235 AC: 2481 AN: 10578

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21017 AN: 67962

Other (OTH) AF: 0.323 AC: 682 AN: 2112

Alfa AF: 0.220 Hom.: 777

Bravo AF: 0.327

Asia WGS AF: 0.492 AC: 1708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.44
PhyloP100		0.081
PromoterAI		0.0038	Neutral
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: rs67261052; hg19: chr3-195956970; COSMIC: COSV53057632; COSMIC: COSV53057632;