X-13594880-A-T

Variant names:

• chrX-13594880-A-T
• NM_015507.4:c.232A>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015507.4(EGFL6):​c.232A>T​(p.Asn78Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000911 in 1,097,410 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: EGFL6 NM_015507.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.08

Genes affected

EGFL6 (HGNC:3235): (EGF like domain multiple 6) This gene encodes a member of the epidermal growth factor (EGF) repeat superfamily. Members of this superfamily are characterized by the presence of EGF-like repeats and are often involved in the regulation of cell cycle, proliferation, and developmental processes. The gene product contains a signal peptide, suggesting that it is secreted; an EGF repeat region consisting of 4 complete EGF-like repeats and 1 partial EGF-like repeat, 3 of which have a calcium-binding consensus sequence; an arg-gly-asp integrin association motif; and a MAM domain, which is believed to have an adhesive function. This gene is expressed early during development, and its expression has been detected in lung and meningioma tumors. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.794

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFL6	NM_015507.4	c.232A>T	p.Asn78Tyr	missense_variant	Exon 3 of 12	ENST00000361306.6	NP_056322.2
EGFL6	NM_001167890.2	c.232A>T	p.Asn78Tyr	missense_variant	Exon 3 of 12		NP_001161362.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFL6	ENST00000361306.6	c.232A>T	p.Asn78Tyr	missense_variant	Exon 3 of 12	1	NM_015507.4	ENSP00000355126.1
EGFL6	ENST00000380602.3	c.232A>T	p.Asn78Tyr	missense_variant	Exon 3 of 12	1		ENSP00000369976.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097410 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 362816

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: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T;.
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.86	D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	-0.88	N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-7.4	D;D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0010	D;D
Sift4G	Benign	0.086	T;T
Polyphen		0.91	P;D
Vest4		0.77
MutPred		0.50		Loss of disorder (P = 0.0738);Loss of disorder (P = 0.0738);
MVP		0.72
MPC		0.74
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.91
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chrX-13612999;