19-5688100-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198533.3(HSD11B1L):​c.853C>T​(p.His285Tyr) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

HSD11B1L
NM_198533.3 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.647
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HSD11B1LNM_198706.3 linkc.*155C>T 3_prime_UTR_variant Exon 8 of 8 ENST00000339423.7 NP_941995.1 Q7Z5J1-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HSD11B1LENST00000339423.7 linkc.*155C>T 3_prime_UTR_variant Exon 8 of 8 1 NM_198706.3 ENSP00000340436.2 Q7Z5J1-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.853C>T (p.H285Y) alteration is located in exon 8 (coding exon 7) of the HSD11B1L gene. This alteration results from a C to T substitution at nucleotide position 853, causing the histidine (H) at amino acid position 285 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.028
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
9.7
DANN
Benign
0.80
DEOGEN2
Benign
0.0037
.;.;T
Eigen
Benign
-0.83
Eigen_PC
Benign
-0.92
FATHMM_MKL
Benign
0.029
N
LIST_S2
Benign
0.40
T;T;T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.097
T;T;T
MetaSVM
Benign
-0.62
T
MutationAssessor
Benign
0.0
.;.;N
PROVEAN
Benign
-0.40
.;N;N
REVEL
Benign
0.21
Sift
Benign
0.036
.;D;D
Sift4G
Uncertain
0.032
D;D;D
Polyphen
0.72
P;.;B
Vest4
0.15
MutPred
0.32
.;.;Gain of phosphorylation at H285 (P = 0.005);
MVP
0.62
MPC
0.74
ClinPred
0.12
T
GERP RS
1.8
Varity_R
0.082

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.53
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.53
Position offset: -2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs769857104; hg19: chr19-5688111; API