rs145508592

Variant names:

• chr19-5687363-T-C
• rs145508592
• NM_198706.3:c.490T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-5687363-T-C
• chr19-5687363-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_198706.3(HSD11B1L):​c.490T>C​(p.Ser164Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HSD11B1L NM_198706.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.73
• Publications: 0 publications found

Genes affected

HSD11B1L (HGNC:30419): (hydroxysteroid 11-beta dehydrogenase 1 like) This gene is a member of the hydroxysteroid dehydrogenase family. The encoded protein is similar to an enzyme that catalyzes the interconversion of inactive to active glucocorticoids (e.g. cortisone). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2012]

RPL36 (HGNC:13631): (ribosomal protein L36) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L36E family of ribosomal proteins. It is located in the cytoplasm. Transcript variants derived from alternative splicing exist; they encode the same protein. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.917

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198706.3. 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
	HSD11B1L	NM_198706.3	MANE Select	c.490T>C	p.Ser164Pro	missense	Exon 6 of 8	NP_941995.1	Q7Z5J1-2
	HSD11B1L	NM_001267868.2		c.631T>C	p.Ser211Pro	missense	Exon 7 of 9	NP_001254797.1	A0A087WWR3
	HSD11B1L	NM_198533.3		c.490T>C	p.Ser164Pro	missense	Exon 6 of 8	NP_940935.1	Q7Z5J1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B1L	ENST00000339423.7	TSL:1 MANE Select	c.490T>C	p.Ser164Pro	missense	Exon 6 of 8	ENSP00000340436.2	Q7Z5J1-2
	HSD11B1L	ENST00000423665.6	TSL:1	c.490T>C	p.Ser164Pro	missense	Exon 6 of 8	ENSP00000407154.2	Q7Z5J1-1
	HSD11B1L	ENST00000581773.5	TSL:1	c.490T>C	p.Ser164Pro	missense	Exon 7 of 9	ENSP00000462975.1	Q7Z5J1-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.82	D
Eigen	Uncertain	0.37
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.022	N
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.088	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Pathogenic	0.97	D
MutationAssessor	Pathogenic	4.0	H
PhyloP100		1.7
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-4.6	D
REVEL	Pathogenic	0.90
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.21	T
Polyphen		1.0	D
Vest4		0.67
MutPred		0.85		Gain of sheet (P = 0.0344)
MVP		0.89
MPC		1.8
ClinPred		1.0	D
GERP RS		1.9
Varity_R		0.81
gMVP		0.98
Mutation Taster		=69/31	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: rs145508592; hg19: chr19-5687374;