chr3-196226982-C-A

Variant names:

• chr3-196226982-C-A
• rs1260763347
• NM_152672.6:c.151C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_152672.6(SLC51A):​c.151C>A​(p.Leu51Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC51A NM_152672.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.482
• 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: 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034563094).
• BP6: Variant 3-196226982-C-A is Benign according to our data. Variant chr3-196226982-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2241883.Status of the report is criteria_provided_single_submitter, 1 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.151C>A	p.Leu51Ile	missense	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.151C>A	p.Leu51Ile	missense	Exon 3 of 9	ENSP00000296327.5	Q86UW1
	SLC51A	ENST00000900647.1		c.151C>A	p.Leu51Ile	missense	Exon 4 of 10	ENSP00000570706.1
	SLC51A	ENST00000900649.1		c.151C>A	p.Leu51Ile	missense	Exon 3 of 10	ENSP00000570708.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461390 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727062

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111720

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.68
DANN	Benign	0.83
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.3	N
PhyloP100		0.48
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.020
Sift	Benign	1.0	T
Sift4G	Benign	0.75	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.32		Loss of helix (P = 0.0558)
MVP		0.072
MPC		0.14
ClinPred		0.036	T
GERP RS		-1.5
Varity_R		0.053
gMVP		0.24
Mutation Taster		=100/0	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: rs1260763347; hg19: chr3-195953853;