chr6-32167161-G-T

Variant names:

• chr6-32167161-G-T
• NM_030652.4:c.505G>T

Variant summary

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

The NM_030652.4(EGFL8):​c.505G>T​(p.Gly169Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,728 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EGFL8 NM_030652.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.586

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFL8	NM_030652.4	c.505G>T	p.Gly169Cys	missense_variant	Exon 6 of 9	ENST00000333845.11	NP_085155.1
EGFL8	NR_037860.2	n.620G>T		non_coding_transcript_exon_variant	Exon 6 of 9
PPT2-EGFL8	NR_037861.1	n.2022G>T		non_coding_transcript_exon_variant	Exon 13 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFL8	ENST00000333845.11	c.505G>T	p.Gly169Cys	missense_variant	Exon 6 of 9	1	NM_030652.4	ENSP00000333380.6
PPT2-EGFL8	ENST00000422437.5	n.*421G>T		non_coding_transcript_exon_variant	Exon 14 of 21	5		ENSP00000457534.1
PPT2-EGFL8	ENST00000422437.5	n.*421G>T		3_prime_UTR_variant	Exon 14 of 21	5		ENSP00000457534.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460728 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726672

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T;.
Eigen	Benign	-0.062
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.42	N
LIST_S2	Uncertain	0.94	.;D;T
M_CAP	Pathogenic	0.35	D
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Uncertain	2.4	M;M;.
PROVEAN	Benign	-1.0	N;N;N
REVEL	Uncertain	0.42
Sift	Benign	0.056	T;T;D
Sift4G	Uncertain	0.052	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.36
MutPred		0.30		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;
MVP		0.98
MPC		1.2
ClinPred		0.76	D
GERP RS		-0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr6-32134938;