chrX-13594871-G-A

Position:

• chrX-13594871-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_015507.4(EGFL6):​c.223G>A​(p.Val75Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00657 in 1,209,135 control chromosomes in the GnomAD database, including 31 homozygotes. There are 2,527 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0055 (4 hom., 193 hem., cov: 23)
  • Exomes 𝑓: 0.0067 (27 hom. 2334 hem.)
• Consequence: EGFL6 NM_015507.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.10

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008598298).
• BP6: Variant X-13594871-G-A is Benign according to our data. Variant chrX-13594871-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 789545.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFL6	NM_015507.4	c.223G>A	p.Val75Met	missense_variant	3/12	ENST00000361306.6
EGFL6	NM_001167890.2	c.223G>A	p.Val75Met	missense_variant	3/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFL6	ENST00000361306.6	c.223G>A	p.Val75Met	missense_variant	3/12	1	NM_015507.4	A2
EGFL6	ENST00000380602.3	c.223G>A	p.Val75Met	missense_variant	3/12	1		P4

Frequencies

GnomAD3 genomes AF: 0.00552 AC: 617 AN: 111786 Hom.: 4 Cov.: 23 AF XY: 0.00568 AC XY: 193 AN XY: 33980

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00617

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000746

Gnomad FIN AF: 0.00777

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00797

Gnomad OTH AF: 0.00674

GnomAD3 exomes AF: 0.00427 AC: 781 AN: 183011 Hom.: 2 AF XY: 0.00403 AC XY: 272 AN XY: 67517

Gnomad AFR exome AF: 0.00107

Gnomad AMR exome AF: 0.00117

Gnomad ASJ exome AF: 0.00816

Gnomad EAS exome AF: 0.0000723

Gnomad SAS exome AF: 0.000631

Gnomad FIN exome AF: 0.00656

Gnomad NFE exome AF: 0.00656

Gnomad OTH exome AF: 0.00443

GnomAD4 exome AF: 0.00667 AC: 7322 AN: 1097295 Hom.: 27 Cov.: 29 AF XY: 0.00643 AC XY: 2334 AN XY: 362723

Gnomad4 AFR exome AF: 0.000606

Gnomad4 AMR exome AF: 0.00179

Gnomad4 ASJ exome AF: 0.00837

Gnomad4 EAS exome AF: 0.0000662

Gnomad4 SAS exome AF: 0.00109

Gnomad4 FIN exome AF: 0.00755

Gnomad4 NFE exome AF: 0.00766

Gnomad4 OTH exome AF: 0.00569

GnomAD4 genome AF: 0.00551 AC: 616 AN: 111840 Hom.: 4 Cov.: 23 AF XY: 0.00567 AC XY: 193 AN XY: 34044

Gnomad4 AFR AF: 0.00120

Gnomad4 AMR AF: 0.00616

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000748

Gnomad4 FIN AF: 0.00777

Gnomad4 NFE AF: 0.00795

Gnomad4 OTH AF: 0.00665

Alfa AF: 0.00695 Hom.: 116

Bravo AF: 0.00529

TwinsUK AF: 0.0102 AC: 38

ALSPAC AF: 0.0104 AC: 30

ESP6500AA AF: 0.00209 AC: 8

ESP6500EA AF: 0.00788 AC: 53

ExAC AF: 0.00471 AC: 572

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0088	T;.
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.25	T;T
MetaRNN	Benign	0.0086	T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	0.98	D;D
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.9	N;N
REVEL	Uncertain	0.32
Sift	Benign	0.086	T;T
Sift4G	Benign	0.070	T;T
Polyphen		0.71	P;D
Vest4		0.15
MVP		0.74
MPC		0.79
ClinPred		0.012	T
GERP RS		4.1
Varity_R		0.13
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs141324039; hg19: chrX-13612990;