19-5687932-C-G

Variant names:

• chr19-5687932-C-G
• rs763669331
• NM_198706.3:c.848C>G

Variant summary

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

The NM_198706.3(HSD11B1L):​c.848C>G​(p.Ala283Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000425 in 1,410,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. A283V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: HSD11B1L NM_198706.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• 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=0.07579878).

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.848C>G	p.Ala283Gly	missense	Exon 8 of 8	NP_941995.1	Q7Z5J1-2
	HSD11B1L	NM_001267868.2		c.989C>G	p.Ala330Gly	missense	Exon 9 of 9	NP_001254797.1	A0A087WWR3
	HSD11B1L	NM_198533.3		c.685C>G	p.Pro229Ala	missense	Exon 8 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.848C>G	p.Ala283Gly	missense	Exon 8 of 8	ENSP00000340436.2	Q7Z5J1-2
	HSD11B1L	ENST00000423665.6	TSL:1	c.685C>G	p.Pro229Ala	missense	Exon 8 of 8	ENSP00000407154.2	Q7Z5J1-1
	HSD11B1L	ENST00000581773.5	TSL:1	c.848C>G	p.Ala283Gly	missense	Exon 9 of 9	ENSP00000462975.1	Q7Z5J1-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000598 AC: 1 AN: 167230 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000425 AC: 6 AN: 1410704 Hom.: 0 Cov.: 33 AF XY: 0.00000430 AC XY: 3 AN XY: 697522

African (AFR) AF: 0.00 AC: 0 AN: 31938

American (AMR) AF: 0.00 AC: 0 AN: 38604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25454

East Asian (EAS) AF: 0.00 AC: 0 AN: 36384

South Asian (SAS) AF: 0.0000742 AC: 6 AN: 80816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085230

Other (OTH) AF: 0.00 AC: 0 AN: 58338

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	13
DANN	Benign	0.90
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.81	T
PhyloP100		1.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.096
Sift	Uncertain	0.028	D
Sift4G	Benign	0.071	T
Polyphen		0.15	B
Vest4		0.11
MutPred		0.35		Gain of catalytic residue at A283 (P = 0.0405)
MVP		0.46
ClinPred		0.091	T
GERP RS		0.64
Varity_R		0.025
gMVP		0.62
Mutation Taster		=93/7	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: rs763669331; hg19: chr19-5687943;