rs328694

chr5-119634265-C-Achr5-119634265-C-Gchr5-119634265-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/20 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. P173S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM170A NM_001367956.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.996

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.176804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM170A	NM_001367956.1	c.517C>A	p.Pro173Thr	missense_variant	3/5	ENST00000695508.1
FAM170A	NM_182761.4	c.517C>A	p.Pro173Thr	missense_variant	3/5
FAM170A	NM_001163991.2	c.376C>A	p.Pro126Thr	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM170A	ENST00000695508.1	c.517C>A	p.Pro173Thr	missense_variant	3/5		NM_001367956.1	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.63	T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.5	M;.;M
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.34	T
Sift4G	Benign	0.40	T;T;T
Polyphen		1.0	.;.;D
Vest4		0.36
MutPred		0.21		Loss of catalytic residue at P172 (P = 0.0175);.;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

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

LitVar

Other links and lift over

dbSNP: rs328694; hg19: chr5-118969960;