5-119632795-GTG-TTA

Variant names:

• chr5-119632795-GTG-TTA
• NM_001367956.1:c.118_120delGTGinsTTA
• FAM170A p.Val40Leu

Variant summary

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

The NM_001367956.1(FAM170A):​c.118_120delGTGinsTTA​(p.Val40Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. V40M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM170A NM_001367956.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.118_120delGTGinsTTA	p.Val40Leu	missense	N/A	NP_001354885.1	A1A519-1
	FAM170A	NM_182761.4		c.118_120delGTGinsTTA	p.Val40Leu	missense	N/A	NP_877438.2	A1A519-2
	FAM170A	NM_001163991.2		c.71-1165_71-1163delGTGinsTTA		intron	N/A	NP_001157463.1	A1A519-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM170A	ENST00000695508.1	MANE Select	c.118_120delGTGinsTTA	p.Val40Leu	missense	N/A	ENSP00000511971.1	A1A519-1
	FAM170A	ENST00000335286.10	TSL:1	c.118_120delGTGinsTTA	p.Val40Leu	missense	N/A	ENSP00000334285.6	A1A519-2
	FAM170A	ENST00000379555.7	TSL:1	c.71-1165_71-1163delGTGinsTTA		intron	N/A	ENSP00000368873.3	A1A519-3

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-118968490;