NM_001367956.1:c.517C>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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_001367956.1:c.517C>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