rs770225679

Variant names:

• chr4-87390886-T-C
• rs770225679
• NM_016245.5:c.185A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-87390886-T-C
• chr4-87390886-T-G

Variant summary

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

The NM_016245.5(HSD17B11):​c.185A>G​(p.Lys62Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. 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. K62T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: HSD17B11 NM_016245.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.104
• Publications: 0 publications found

Genes affected

HSD17B11 (HGNC:22960): (hydroxysteroid 17-beta dehydrogenase 11) Short-chain alcohol dehydrogenases, such as HSD17B11, metabolize secondary alcohols and ketones (Brereton et al., 2001 [PubMed 11165019]).[supplied by OMIM, Jun 2009]

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=0.08946374).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016245.5. 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
	HSD17B11	NM_016245.5	MANE Select	c.185A>G	p.Lys62Arg	missense	Exon 1 of 7	NP_057329.3	Q8NBQ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B11	ENST00000358290.9	TSL:1 MANE Select	c.185A>G	p.Lys62Arg	missense	Exon 1 of 7	ENSP00000351035.4	Q8NBQ5
	HSD17B11	ENST00000854937.1		c.185A>G	p.Lys62Arg	missense	Exon 1 of 7	ENSP00000524996.1
	HSD17B11	ENST00000854933.1		c.185A>G	p.Lys62Arg	missense	Exon 1 of 7	ENSP00000524992.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461838 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727220

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111958

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

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	0.087
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.93
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.85	T
PhyloP100		0.10
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.20
Sift	Benign	0.81	T
Sift4G	Benign	0.76	T
Vest4		0.13
MutPred		0.41		Gain of MoRF binding (P = 0.0568)
MVP		0.46
MPC		0.25
ClinPred		0.11	T
GERP RS		2.1
PromoterAI		-0.13	Neutral
gMVP		0.20
Mutation Taster		=81/19	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: rs770225679; hg19: chr4-88312038;