NM_198706.3:c.848C>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_198706.3(HSD11B1L):​c.848C>T​(p.Ala283Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000608 in 1,563,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000061 (0 hom.)
• Consequence: HSD11B1L NM_198706.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01786822).

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>T	p.Ala283Val	missense	Exon 8 of 8	NP_941995.1	Q7Z5J1-2
	HSD11B1L	NM_001267868.2		c.989C>T	p.Ala330Val	missense	Exon 9 of 9	NP_001254797.1	A0A087WWR3
	HSD11B1L	NM_198533.3		c.685C>T	p.Pro229Ser	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>T	p.Ala283Val	missense	Exon 8 of 8	ENSP00000340436.2	Q7Z5J1-2
	HSD11B1L	ENST00000423665.6	TSL:1	c.685C>T	p.Pro229Ser	missense	Exon 8 of 8	ENSP00000407154.2	Q7Z5J1-1
	HSD11B1L	ENST00000581773.5	TSL:1	c.848C>T	p.Ala283Val	missense	Exon 9 of 9	ENSP00000462975.1	Q7Z5J1-2

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152248 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000132 AC: 22 AN: 167230 AF XY: 0.000188

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000247

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000610 AC: 86 AN: 1410704 Hom.: 0 Cov.: 33 AF XY: 0.0000860 AC XY: 60 AN XY: 697522

African (AFR) AF: 0.0000313 AC: 1 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: 0.0000825 AC: 3 AN: 36384

South Asian (SAS) AF: 0.000829 AC: 67 AN: 80816

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

Middle Eastern (MID) AF: 0.000875 AC: 5 AN: 5714

European-Non Finnish (NFE) AF: 0.00000461 AC: 5 AN: 1085230

Other (OTH) AF: 0.0000857 AC: 5 AN: 58338

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152366 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74512

African (AFR) AF: 0.0000721 AC: 3 AN: 41602

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.000104 AC: 12

Asia WGS AF: 0.000289 AC: 1 AN: 3476

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	0.071
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	8.6
DANN	Uncertain	0.98
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-0.83	T
PhyloP100		1.1
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.14
Sift	Uncertain	0.021	D
Sift4G	Benign	0.079	T
Polyphen		0.016	B
Vest4		0.094
MutPred		0.37		Loss of disorder (P = 0.0695)
MVP		0.44
ClinPred		0.016	T
GERP RS		0.64
Varity_R		0.028
gMVP		0.70
Mutation Taster		=95/5	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;