6-22569663-G-C

Position:

• chr6-22569663-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138574.4(HDGFL1):​c.88G>C​(p.Glu30Gln) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HDGFL1 NM_138574.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.68

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]

CASC15 (HGNC:):

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=0.26300317).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDGFL1	NM_138574.4	c.88G>C	p.Glu30Gln	missense_variant	1/1	ENST00000510882.4	NP_612641.2
LOC105374971	XR_001744025.1	n.489-4456G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDGFL1	ENST00000510882.4	c.88G>C	p.Glu30Gln	missense_variant	1/1	6	NM_138574.4	ENSP00000442129.1
CASC15	ENST00000652081.1	n.146-4456G>C		intron_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2023

The c.88G>C (p.E30Q) alteration is located in exon 1 (coding exon 1) of the HDGFL1 gene. This alteration results from a G to C substitution at nucleotide position 88, causing the glutamic acid (E) at amino acid position 30 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.37	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	2.0	M
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.25
Sift	Benign	0.046	D
Sift4G	Uncertain	0.014	D
Polyphen		0.95	P
Vest4		0.22
MutPred		0.51		Gain of MoRF binding (P = 0.0309);
MVP		0.61
MPC		1.4
ClinPred		0.87	D
GERP RS		0.40
Varity_R		0.075
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-22569892;