NM_198706.3:c.151C>T

Variant names:

• chr19-5685066-C-T
• rs535314623
• NM_198706.3:c.151C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_198706.3(HSD11B1L):​c.151C>T​(p.Arg51Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,554,742 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R51H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: HSD11B1L NM_198706.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.683
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.151C>T	p.Arg51Cys	missense	Exon 3 of 8	NP_941995.1	Q7Z5J1-2
	HSD11B1L	NM_001267868.2		c.292C>T	p.Arg98Cys	missense	Exon 4 of 9	NP_001254797.1	A0A087WWR3
	HSD11B1L	NM_198533.3		c.151C>T	p.Arg51Cys	missense	Exon 3 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.151C>T	p.Arg51Cys	missense	Exon 3 of 8	ENSP00000340436.2	Q7Z5J1-2
	HSD11B1L	ENST00000423665.6	TSL:1	c.151C>T	p.Arg51Cys	missense	Exon 3 of 8	ENSP00000407154.2	Q7Z5J1-1
	HSD11B1L	ENST00000581773.5	TSL:1	c.151C>T	p.Arg51Cys	missense	Exon 4 of 9	ENSP00000462975.1	Q7Z5J1-2

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000125 AC: 2 AN: 159812 AF XY: 0.0000237

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000160

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000150 AC: 21 AN: 1402468 Hom.: 0 Cov.: 32 AF XY: 0.00000867 AC XY: 6 AN XY: 692400

African (AFR) AF: 0.0000315 AC: 1 AN: 31742

American (AMR) AF: 0.0000277 AC: 1 AN: 36058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25214

East Asian (EAS) AF: 0.00 AC: 0 AN: 35900

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 80016

European-Finnish (FIN) AF: 0.0000206 AC: 1 AN: 48572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5614

European-Non Finnish (NFE) AF: 0.0000139 AC: 15 AN: 1081142

Other (OTH) AF: 0.0000344 AC: 2 AN: 58210

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74448

African (AFR) AF: 0.0000481 AC: 2 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000440 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000185 AC: 2

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	Benign	0.20
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Benign	0.87
DEOGEN2	Uncertain	0.77	D
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.065
FATHMM_MKL	Benign	0.62	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		0.68
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.50
MutPred		0.45		Gain of catalytic residue at L52 (P = 0.0071)
MVP		0.77
MPC		1.9
ClinPred		0.97	D
GERP RS		2.4
PromoterAI		0.0075	Neutral
Varity_R		0.52
gMVP		0.64
Mutation Taster		=83/17	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: rs535314623; hg19: chr19-5685077;