NM_178135.5:c.716C>T

Variant names:

• chr4-87310339-G-A
• rs111403391
• NM_178135.5:c.716C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_178135.5(HSD17B13):​c.716C>T​(p.Thr239Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,561,420 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (44 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (25 hom.)
• Consequence: HSD17B13 NM_178135.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.73
• Publications: 3 publications found

Genes affected

HSD17B13 (HGNC:18685): (hydroxysteroid 17-beta dehydrogenase 13) Predicted to enable oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor and steroid dehydrogenase activity. Acts upstream of or within positive regulation of lipid biosynthetic process. Located in lipid droplet. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030733347).
• BP6: Variant 4-87310339-G-A is Benign according to our data. Variant chr4-87310339-G-A is described in ClinVar as [Benign]. Clinvar id is 711910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0115 (1756/152106) while in subpopulation AFR AF = 0.0408 (1691/41488). AF 95% confidence interval is 0.0391. There are 44 homozygotes in GnomAd4. There are 829 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B13	NM_178135.5	c.716C>T	p.Thr239Ile	missense_variant	Exon 6 of 7	ENST00000328546.5	NP_835236.2
HSD17B13	NM_001136230.3	c.608C>T	p.Thr203Ile	missense_variant	Exon 5 of 6		NP_001129702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B13	ENST00000328546.5	c.716C>T	p.Thr239Ile	missense_variant	Exon 6 of 7	1	NM_178135.5	ENSP00000333300.4
HSD17B13	ENST00000302219.10	c.608C>T	p.Thr203Ile	missense_variant	Exon 5 of 6	1		ENSP00000305438.6

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1751 AN: 151988 Hom.: 44 Cov.: 32

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00528

GnomAD2 exomes AF: 0.00270 AC: 541 AN: 200490 AF XY: 0.00202

Gnomad AFR exome AF: 0.0386

Gnomad AMR exome AF: 0.00122

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000309

Gnomad OTH exome AF: 0.000665

GnomAD4 exome AF: 0.00117 AC: 1642 AN: 1409314 Hom.: 25 Cov.: 33 AF XY: 0.00106 AC XY: 740 AN XY: 700492

African (AFR) AF: 0.0455 AC: 1353 AN: 29736

American (AMR) AF: 0.00122 AC: 40 AN: 32732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24590

East Asian (EAS) AF: 0.00 AC: 0 AN: 36452

South Asian (SAS) AF: 0.000117 AC: 9 AN: 76884

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52700

Middle Eastern (MID) AF: 0.00146 AC: 8 AN: 5476

European-Non Finnish (NFE) AF: 0.0000760 AC: 83 AN: 1092598

Other (OTH) AF: 0.00256 AC: 149 AN: 58146

GnomAD4 genome AF: 0.0115 AC: 1756 AN: 152106 Hom.: 44 Cov.: 32 AF XY: 0.0112 AC XY: 829 AN XY: 74348

African (AFR) AF: 0.0408 AC: 1691 AN: 41488

American (AMR) AF: 0.00301 AC: 46 AN: 15282

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: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68012

Other (OTH) AF: 0.00523 AC: 11 AN: 2104

Alfa AF: 0.00402 Hom.: 19

Bravo AF: 0.0132

ESP6500AA AF: 0.0348 AC: 153

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00364 AC: 442

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 18, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	.;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.68	T;T
MetaRNN	Benign	0.0031	T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.0	.;L
PhyloP100		2.7
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.8	N;N
REVEL	Uncertain	0.30
Sift	Benign	0.049	D;D
Sift4G	Uncertain	0.038	D;D
Polyphen		0.016	B;B
Vest4		0.29
MVP		0.89
MPC		0.12
ClinPred		0.020	T
GERP RS		4.3
Varity_R		0.081
gMVP		0.46
Mutation Taster		=98/2	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: rs111403391; hg19: chr4-88231491;