6-32166733-G-C

Variant names:

• chr6-32166733-G-C
• NM_030652.4:c.257G>C

Variant summary

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

The NM_030652.4(EGFL8):​c.257G>C​(p.Arg86Thr) 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. 14/20 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. R86K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EGFL8 NM_030652.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56

Genes affected

EGFL8 (HGNC:13944): (EGF like domain multiple 8) Predicted to enable signaling receptor binding activity. Predicted to be involved in anatomical structure development. Predicted to act upstream of or within in utero embryonic development. Predicted to be active in cell surface and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

PPT2-EGFL8 (HGNC:48343): (PPT2-EGFL8 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring PPT2 (palmitoyl-protein thioesterase 2) and EGFL8 (EGF-like-domain, multiple 8) genes located in the major histocompatibility complex class III region of chromosome 6. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

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=0.17134923).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFL8	NM_030652.4	c.257G>C	p.Arg86Thr	missense_variant	Exon 4 of 9	ENST00000333845.11	NP_085155.1
EGFL8	NR_037860.2	n.372G>C		non_coding_transcript_exon_variant	Exon 4 of 9
PPT2-EGFL8	NR_037861.1	n.1774G>C		non_coding_transcript_exon_variant	Exon 11 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFL8	ENST00000333845.11	c.257G>C	p.Arg86Thr	missense_variant	Exon 4 of 9	1	NM_030652.4	ENSP00000333380.6
PPT2-EGFL8	ENST00000422437.5	n.*189G>C		non_coding_transcript_exon_variant	Exon 12 of 21	5		ENSP00000457534.1
PPT2-EGFL8	ENST00000422437.5	n.*189G>C		3_prime_UTR_variant	Exon 12 of 21	5		ENSP00000457534.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.0061	T;T;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.70	.;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;L;.
PROVEAN	Benign	-0.89	N;N;N
REVEL	Benign	0.19
Sift	Benign	0.59	T;T;T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.55	P;P;.
Vest4		0.46
MutPred		0.47		Loss of MoRF binding (P = 0.0329);Loss of MoRF binding (P = 0.0329);Loss of MoRF binding (P = 0.0329);
MVP		0.38
MPC		1.3
ClinPred		0.68	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.68

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: chr6-32134510;