19-5687363-T-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD11B1L	NM_198706.3	c.490T>C	p.Ser164Pro	missense_variant	Exon 6 of 8	ENST00000339423.7	NP_941995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD11B1L	ENST00000339423.7	c.490T>C	p.Ser164Pro	missense_variant	Exon 6 of 8	1	NM_198706.3	ENSP00000340436.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 04, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.490T>C (p.S164P) alteration is located in exon 6 (coding exon 5) of the HSD11B1L gene. This alteration results from a T to C substitution at nucleotide position 490, causing the serine (S) at amino acid position 164 to be replaced by a proline (P). 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	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;.;D;D;.;D;D;D;.;D;D
M_CAP	Uncertain	0.088	D
MetaRNN	Pathogenic	0.92	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Pathogenic	0.97	D
MutationAssessor	Pathogenic	4.0	.;.;.;.;H;H;.;.;H;H;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-4.6	.;.;D;D;.;D;.;D;.;D;.
REVEL	Pathogenic	0.90
Sift	Uncertain	0.0010	.;.;D;D;.;D;.;D;.;D;.
Sift4G	Benign	0.21	T;D;D;T;T;T;D;T;T;T;T
Polyphen		1.0	D;P;.;D;D;D;P;D;D;D;.
Vest4		0.67
MutPred		0.85		.;.;.;.;Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);.;.;Gain of sheet (P = 0.0344);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-5687374;