5-119634088-G-A

Variant names:

• chr5-119634088-G-A
• rs764229928
• NM_001367956.1:c.340G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001367956.1(FAM170A):​c.340G>A​(p.Val114Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: FAM170A NM_001367956.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.542
• Publications: 0 publications found

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]

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: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen
• Perrault syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Perrault syndrome 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.094993114).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367956.1. 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
	FAM170A	NM_001367956.1	MANE Select	c.340G>A	p.Val114Met	missense	Exon 3 of 5	NP_001354885.1	A1A519-1
	FAM170A	NM_182761.4		c.340G>A	p.Val114Met	missense	Exon 3 of 5	NP_877438.2	A1A519-2
	FAM170A	NM_001163991.2		c.199G>A	p.Val67Met	missense	Exon 2 of 4	NP_001157463.1	A1A519-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM170A	ENST00000695508.1	MANE Select	c.340G>A	p.Val114Met	missense	Exon 3 of 5	ENSP00000511971.1	A1A519-1
	FAM170A	ENST00000335286.10	TSL:1	c.340G>A	p.Val114Met	missense	Exon 3 of 5	ENSP00000334285.6	A1A519-2
	FAM170A	ENST00000379555.7	TSL:1	c.199G>A	p.Val67Met	missense	Exon 2 of 4	ENSP00000368873.3	A1A519-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000361 AC: 9 AN: 249544 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461890 Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 6 AN XY: 727244

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: 0.000174 AC: 15 AN: 86258

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: 8.99e-7 AC: 1 AN: 1112008

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

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000248 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.13
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.54
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.062
Sift	Uncertain	0.022	D
Sift4G	Benign	0.19	T
Polyphen		0.96	D
Vest4		0.27
MutPred		0.31		Loss of sheet (P = 0.0457)
MVP		0.030
ClinPred		0.29	T
GERP RS		0.47
Varity_R		0.062
gMVP		0.089
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs764229928; hg19: chr5-118969783;