dbSNP rs148913870: SLC51A:p.Pro3Pro (chr3-196216721-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7

The NM_152672.6(SLC51A):c.9G>A(p.Pro3Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000099 in 1,575,280 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).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000062 ( 1 hom. )

Consequence

SLC51A
NM_152672.6 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.382

Publications

0 publications found

Variant links:

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]

SLC51A links:

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

PCYT1A links:

LOC105374304 (HGNC:):

LOC105374304 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 3-196216721-G-A is Benign according to our data. Variant chr3-196216721-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3053923.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.382 with no splicing effect.

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.9G>A	p.Pro3Pro	synonymous	Exon 1 of 9	NP_689885.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC51A	ENST00000296327.10	TSL:1 MANE Select	c.9G>A	p.Pro3Pro	synonymous	Exon 1 of 9	ENSP00000296327.5	Q86UW1
SLC51A	ENST00000900647.1		c.9G>A	p.Pro3Pro	synonymous	Exon 2 of 10	ENSP00000570706.1
SLC51A	ENST00000900649.1		c.9G>A	p.Pro3Pro	synonymous	Exon 1 of 10	ENSP00000570708.1

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000215

AC:

AN:

185998

AF XY:

0.000169

show subpopulations

Gnomad AFR exome

AF:

0.00240

Gnomad AMR exome

AF:

0.000239

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000396

Gnomad OTH exome

AF:

0.000410

GnomAD4 exome

AF:

0.0000618

AC:

AN:

1423180

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

704498

show subpopulations

African (AFR)

AF:

0.00150

AC:

AN:

32640

American (AMR)

AF:

0.000274

AC:

AN:

40124

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25486

East Asian (EAS)

AF:

0.00

AC:

AN:

37616

South Asian (SAS)

AF:

0.0000246

AC:

AN:

81322

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49184

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.0000165

AC:

AN:

1092276

Other (OTH)

AF:

0.000119

AC:

AN:

58820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000447

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

41442

American (AMR)

AF:

0.000458

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68004

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000165

Hom.:

Bravo

AF:

0.000570

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

SLC51A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.2

(source)

DANN

Benign

0.93

PhyloP100

-0.38

PromoterAI

0.0010

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over