15-65050082-GT-G

Position:

• chr15-65050082-GT-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_178859.4(SLC51B):​c.84delT​(p.Arg29fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC51B NM_178859.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: -0.819

Genes affected

SLC51B (HGNC:29956): (SLC51 subunit beta) Predicted to enable protein heterodimerization activity and transmembrane transporter activity. Involved in bile acid secretion. Located in basolateral plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RASL12 (HGNC:30289): (RAS like family 12) Predicted to enable GDP binding activity; GTP binding activity; and GTPase activity. Predicted to be involved in signal transduction. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 15-65050082-GT-G is Pathogenic according to our data. Variant chr15-65050082-GT-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 804474.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC51B	NM_178859.4	c.84delT	p.Arg29fs	frameshift_variant	2/4	ENST00000334287.3	NP_849190.2
SLC51B	XM_005254159.6	c.84delT	p.Arg29fs	frameshift_variant	2/4		XP_005254216.1
RASL12	XM_017022296.2	c.*1907delA		3_prime_UTR_variant	5/5		XP_016877785.1
RASL12	XM_005254434.5	c.426-4339delA		intron_variant			XP_005254491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC51B	ENST00000334287.3	c.84delT	p.Arg29fs	frameshift_variant	2/4	2	NM_178859.4	ENSP00000335292.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Cholestasis;C0011991:Diarrhea Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Hadassah Hebrew University Medical Center

Jun 20, 2019

- -

Bile acid malabsorption, primary, 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1595900104; hg19: chr15-65342420;