rs328694

Variant names:

• chr5-119634265-C-A
• rs328694
• NM_001367956.1:c.517C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-119634265-C-A
• chr5-119634265-C-G
• chr5-119634265-C-T

Variant summary

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

The NM_001367956.1(FAM170A):​c.517C>A​(p.Pro173Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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: not found (cov: 32)
• Consequence: FAM170A NM_001367956.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.996
• Publications: 35 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: 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

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=0.176804).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM170A	NM_001367956.1	MANE Select	c.517C>A	p.Pro173Thr	missense	Exon 3 of 5	NP_001354885.1
	FAM170A	NM_182761.4		c.517C>A	p.Pro173Thr	missense	Exon 3 of 5	NP_877438.2
	FAM170A	NM_001163991.2		c.376C>A	p.Pro126Thr	missense	Exon 2 of 4	NP_001157463.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM170A	ENST00000695508.1	MANE Select	c.517C>A	p.Pro173Thr	missense	Exon 3 of 5	ENSP00000511971.1
	FAM170A	ENST00000335286.10	TSL:1	c.517C>A	p.Pro173Thr	missense	Exon 3 of 5	ENSP00000334285.6
	FAM170A	ENST00000379555.7	TSL:1	c.376C>A	p.Pro126Thr	missense	Exon 2 of 4	ENSP00000368873.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 55196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.0
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.094
Sift	Benign	0.18	T
Sift4G	Benign	0.40	T
Polyphen		1.0	D
Vest4		0.36
MutPred		0.21		Loss of catalytic residue at P172 (P = 0.0175)
MVP		0.10
ClinPred		0.87	D
GERP RS		2.1
Varity_R		0.076
gMVP		0.18
Mutation Taster		=100/0	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: rs328694; hg19: chr5-118969960;