Genetic Variant NM_198706.3:c.490T>C (chr19-5687363-T-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

Publications

0 publications found

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]

HSD11B1L links:

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]

RPL36 links:

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ACMG classification

Classification was made for transcript

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

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

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.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.38

BayesDel_noAF

Pathogenic

0.31

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.82

Eigen

Uncertain

0.37

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.022

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.088

MetaRNN

Pathogenic

0.92

MetaSVM

Pathogenic

0.97

MutationAssessor

Pathogenic

4.0

PhyloP100

1.7

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-4.6

REVEL

Pathogenic

0.90

Sift

Uncertain

0.0010

Sift4G

Benign

0.21

Polyphen

1.0

Vest4

0.67

MutPred

0.85

Gain of sheet (P = 0.0344)

MVP

0.89

MPC

1.8

ClinPred

1.0

GERP RS

1.9

Varity_R

0.81

gMVP

0.98

Mutation Taster

=69/31

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over