HSD11B1L p.Pro268Thr

Variant names:

• chr19-5687886-C-A
• NM_198706.3:c.802C>A
• HSD11B1L p.Pro268Thr

Your query was ambiguous. Multiple possible variants found:

• chr19-5687886-C-A
• chr19-5687886-CCG-ACT
• chr19-5687886-CCG-ACC
• chr19-5687886-CCG-ACA

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_198706.3(HSD11B1L):​c.802C>A​(p.Pro268Thr) 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 benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HSD11B1L NM_198706.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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.802C>A	p.Pro268Thr	missense	Exon 8 of 8	NP_941995.1	Q7Z5J1-2
	HSD11B1L	NM_001267868.2		c.943C>A	p.Pro315Thr	missense	Exon 9 of 9	NP_001254797.1	A0A087WWR3
	HSD11B1L	NM_198705.3		c.559C>A	p.Pro187Thr	missense	Exon 6 of 6	NP_941994.1	Q7Z5J1-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B1L	ENST00000339423.7	TSL:1 MANE Select	c.802C>A	p.Pro268Thr	missense	Exon 8 of 8	ENSP00000340436.2	Q7Z5J1-2
	HSD11B1L	ENST00000581773.5	TSL:1	c.802C>A	p.Pro268Thr	missense	Exon 9 of 9	ENSP00000462975.1	Q7Z5J1-2
	HSD11B1L	ENST00000301382.8	TSL:1	c.559C>A	p.Pro187Thr	missense	Exon 6 of 6	ENSP00000301382.4	Q7Z5J1-6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1427752 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 707948

African (AFR) AF: 0.00 AC: 0 AN: 32524

American (AMR) AF: 0.00 AC: 0 AN: 41780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25634

East Asian (EAS) AF: 0.00 AC: 0 AN: 37482

South Asian (SAS) AF: 0.00 AC: 0 AN: 82612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095740

Other (OTH) AF: 0.00 AC: 0 AN: 58916

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.98	T
PhyloP100		0.52
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.065
Sift	Benign	0.050	D
Sift4G	Uncertain	0.0040	D
La Branchor		0.54
BranchPoint Hunter		4.0
gMVP		0.94
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.59		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.59		Position offset: 30

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-5687897;