19-5688049-C-A

Variant names:

• chr19-5688049-C-A
• rs868141486
• ENST00000423665.6:c.802C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198533.3(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. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P268A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSD11B1L NM_198533.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07790667).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198533.3. 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.*104C>A		3_prime_UTR	Exon 8 of 8	NP_941995.1	Q7Z5J1-2
	HSD11B1L	NM_198533.3		c.802C>A	p.Pro268Thr	missense	Exon 8 of 8	NP_940935.1	Q7Z5J1-1
	HSD11B1L	NM_001267871.2		c.559C>A	p.Pro187Thr	missense	Exon 6 of 6	NP_001254800.1	Q7Z5J1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B1L	ENST00000423665.6	TSL:1	c.802C>A	p.Pro268Thr	missense	Exon 8 of 8	ENSP00000407154.2	Q7Z5J1-1
	HSD11B1L	ENST00000577917.5	TSL:1	c.559C>A	p.Pro187Thr	missense	Exon 6 of 6	ENSP00000463073.1	Q7Z5J1-3
	HSD11B1L	ENST00000411793.6	TSL:1	c.400C>A	p.Pro134Thr	missense	Exon 6 of 6	ENSP00000398955.2	Q7Z5J1-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	1.6
DANN	Benign	0.89
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.0070
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.076
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.012	D
Polyphen		0.48	P
Vest4		0.079
MutPred		0.41		Loss of catalytic residue at P268 (P = 0.0121)
MVP		0.46
MPC		0.71
ClinPred		0.14	T
GERP RS		0.75
Varity_R		0.052
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs868141486; hg19: chr19-5688060;