Variant rs768000933 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138574.4(HDGFL1):c.592C>A(p.Leu198Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,406,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

HDGFL1
NM_138574.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.47

Variant links:

Genes affected

HDGFL1 (HGNC:21095): (HDGF like 1) Predicted to enable double-stranded DNA binding activity and transcription coregulator activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

HDGFL1 links:

CASC15 (HGNC:28245): (cancer susceptibility 15) This gene produces a long non-coding RNA that may regulate cell proliferation. This RNA is upregulated in hepatocellular carcinoma, where it is thought to function as an oncogene. However, some splice variants of this gene may function as a tumor suppressor in neuroblastoma and other tumor types. Circular RNA variants were observed at this gene. [provided by RefSeq, Dec 2017]

CASC15 links:

LOC105374971 (HGNC:):

LOC105374971 links:

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ACMG classification

Classification made for transcript

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=0.1731973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDGFL1	NM_138574.4 link	c.592C>A	p.Leu198Ile	missense_variant	Exon 1 of 1	ENST00000510882.4	NP_612641.2	Q5TGJ6A0A140VJK8
LOC105374971	XR_001744025.1 link	n.489-3952C>A		intron_variant	Intron 5 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDGFL1	ENST00000510882.4 link	c.592C>A	p.Leu198Ile	missense_variant	Exon 1 of 1	6	NM_138574.4	ENSP00000442129.1		Q5TGJ6
CASC15	ENST00000652081.1 link	n.146-3952C>A		intron_variant	Intron 2 of 7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000617

AC:

AN:

162058

Hom.:

AF XY:

0.0000113

AC XY:

AN XY:

88698

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000230

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1406962

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

694852

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.19e-7

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.70

CADD

Benign

5.0

DANN

Benign

0.94

DEOGEN2

Benign

0.0071

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.0028

LIST_S2

Benign

0.30

M_CAP

Benign

0.0064

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.53

REVEL

Benign

0.023

Sift

Benign

0.28

Sift4G

Benign

0.34

Polyphen

0.99

Vest4

0.13

MutPred

0.30

Gain of glycosylation at S195 (P = 0.1108);

MVP

0.15

MPC

1.1

ClinPred

0.51

GERP RS

0.16

Varity_R

0.049

gMVP

0.036

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over