5-119634265-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001367956.1(FAM170A):c.517C>T(p.Pro173Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,613,780 control chromosomes in the GnomAD database, including 162,208 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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. P173L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.42 ( 13716 hom., cov: 32)

Exomes 𝑓: 0.45 ( 148492 hom. )

Consequence

FAM170A
NM_001367956.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.996

Publications

35 publications found

Variant links:

Genes affected

FAM170A (HGNC:27963): (family with sequence similarity 170 member A) Predicted to enable DNA binding activity and metal ion binding activity. Involved in positive regulation of transcription, DNA-templated and transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FAM170A links:

HSD17B4 (HGNC:5213): (hydroxysteroid 17-beta dehydrogenase 4) The protein encoded by this gene is a bifunctional enzyme that is involved in the peroxisomal beta-oxidation pathway for fatty acids. It also acts as a catalyst for the formation of 3-ketoacyl-CoA intermediates from both straight-chain and 2-methyl-branched-chain fatty acids. Defects in this gene that affect the peroxisomal fatty acid beta-oxidation activity are a cause of D-bifunctional protein deficiency (DBPD). An apparent pseudogene of this gene is present on chromosome 8. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]

HSD17B4 Gene-Disease associations (from GenCC):

d-bifunctional protein deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
Perrault syndrome
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
Perrault syndrome 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

HSD17B4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3121963E-4).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM170A	NM_001367956.1 link	c.517C>T	p.Pro173Ser	missense_variant	Exon 3 of 5	ENST00000695508.1	NP_001354885.1
FAM170A	NM_182761.4 link	c.517C>T	p.Pro173Ser	missense_variant	Exon 3 of 5		NP_877438.2	A1A519-2
FAM170A	NM_001163991.2 link	c.376C>T	p.Pro126Ser	missense_variant	Exon 2 of 4		NP_001157463.1	A1A519-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM170A	ENST00000695508.1 link	c.517C>T	p.Pro173Ser	missense_variant	Exon 3 of 5		NM_001367956.1	ENSP00000511971.1		A1A519-1

Frequencies

GnomAD3 genomes

AF:

0.423

AC:

64216

AN:

151882

Hom.:

13716

Cov.:

show subpopulations

Gnomad AFR

AF:

0.348

Gnomad AMI

AF:

0.339

Gnomad AMR

AF:

0.446

Gnomad ASJ

AF:

0.557

Gnomad EAS

AF:

0.510

Gnomad SAS

AF:

0.545

Gnomad FIN

AF:

0.439

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.439

Gnomad OTH

AF:

0.428

GnomAD2 exomes

AF:

0.447

AC:

111530

AN:

249504

AF XY:

0.458

show subpopulations

Gnomad AFR exome

AF:

0.344

Gnomad AMR exome

AF:

0.365

Gnomad ASJ exome

AF:

0.548

Gnomad EAS exome

AF:

0.508

Gnomad FIN exome

AF:

0.431

Gnomad NFE exome

AF:

0.442

Gnomad OTH exome

AF:

0.466

GnomAD4 exome

AF:

0.448

AC:

654971

AN:

1461780

Hom.:

148492

Cov.:

AF XY:

0.453

AC XY:

329088

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.345

AC:

11544

AN:

33474

American (AMR)

AF:

0.372

AC:

16622

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.553

AC:

14445

AN:

26136

East Asian (EAS)

AF:

0.555

AC:

22013

AN:

39698

South Asian (SAS)

AF:

0.545

AC:

46989

AN:

86254

European-Finnish (FIN)

AF:

0.426

AC:

22777

AN:

53420

Middle Eastern (MID)

AF:

0.481

AC:

2773

AN:

5768

European-Non Finnish (NFE)

AF:

0.441

AC:

489807

AN:

1111918

Other (OTH)

AF:

0.464

AC:

28001

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

22379

44759

67138

89518

111897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.423

AC:

64244

AN:

152000

Hom.:

13716

Cov.:

AF XY:

0.429

AC XY:

31877

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.348

AC:

14421

AN:

41464

American (AMR)

AF:

0.446

AC:

6819

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.557

AC:

1930

AN:

3464

East Asian (EAS)

AF:

0.510

AC:

2626

AN:

5146

South Asian (SAS)

AF:

0.545

AC:

2621

AN:

4812

European-Finnish (FIN)

AF:

0.439

AC:

4648

AN:

10576

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.439

AC:

29819

AN:

67938

Other (OTH)

AF:

0.431

AC:

912

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1902

3803

5705

7606

9508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.439

Hom.:

55196

Bravo

AF:

0.418

TwinsUK

AF:

0.444

AC:

1645

ALSPAC

AF:

0.438

AC:

1687

ESP6500AA

AF:

0.341

AC:

1354

ESP6500EA

AF:

0.445

AC:

3719

ExAC

AF:

0.447

AC:

54024

Asia WGS

AF:

0.526

AC:

1834

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

.;.;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.62

T;T;T

MetaRNN

Benign

0.00013

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.8

M;.;M

PhyloP100

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.3

.;.;N

REVEL

Benign

0.093

Sift

Benign

0.27

.;.;T

Sift4G

Benign

0.40

T;T;T

Polyphen

1.0

.;.;D

Vest4

0.090

ClinPred

0.051

GERP RS

2.1

Varity_R

0.058

gMVP

0.22

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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5-119634265-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over