chr19-4502189-T-A

Variant names:

• chr19-4502189-T-A
• rs8887
• NM_001001520.3:c.*179T>A

Variant summary

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

The NM_001348169.2(HDGFL2):​c.*179T>A variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HDGFL2 NM_001348169.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.91
• Publications: 0 publications found

Genes affected

HDGFL2 (HGNC:14680): (HDGF like 2) This gene encodes a member of the hepatoma-derived growth factor (HDGF) family. The protein includes an N-terminal PWWP domain that binds to methyl-lysine-containing histones, with specific binding of this protein to tri-methylated lysines 36 and 79 of histone H3, and di- and tri-methylated lysine 20 of histone H4. The protein functions in LEDGF/p75-independent HIV-1 replication by determining HIV-1 integration site selection. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2014]

PLIN4 (HGNC:29393): (perilipin 4) Members of the perilipin family, such as PLIN4, coat intracellular lipid storage droplets (Wolins et al., 2003 [PubMed 12840023]).[supplied by OMIM, Feb 2010]

PLIN4 Gene-Disease associations (from GenCC):

• vacuolar Neuromyopathy

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

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 (BayesDel_noAF=-0.25).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348169.2. 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
	HDGFL2	NM_001001520.3	MANE Select	c.*179T>A		3_prime_UTR	Exon 16 of 16	NP_001001520.1
	HDGFL2	NM_001348169.2		c.*179T>A		3_prime_UTR	Exon 16 of 16	NP_001335098.1
	HDGFL2	NM_032631.4		c.*179T>A		3_prime_UTR	Exon 16 of 16	NP_116020.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDGFL2	ENST00000616600.5	TSL:1 MANE Select	c.*179T>A		3_prime_UTR	Exon 16 of 16	ENSP00000483345.1
	HDGFL2	ENST00000621835.4	TSL:1	c.*179T>A		3_prime_UTR	Exon 16 of 16	ENSP00000483702.1
	PLIN4	ENST00000901551.1		c.*2270A>T		3_prime_UTR	Exon 8 of 8	ENSP00000571610.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 4

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	14
DANN	Benign	0.90
PhyloP100		2.9

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: rs8887; hg19: chr19-4502201;