X-13594871-G-A

Variant names:

• chrX-13594871-G-A
• rs141324039
• NM_015507.4:c.223G>A

Variant summary

Our verdict is Benign. The variant received -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. 12/20 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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 789545.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015507.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFL6	NM_015507.4	MANE Select	c.223G>A	p.Val75Met	missense	Exon 3 of 12	NP_056322.2
	EGFL6	NM_001167890.2		c.223G>A	p.Val75Met	missense	Exon 3 of 12	NP_001161362.1	Q8IUX8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFL6	ENST00000361306.6	TSL:1 MANE Select	c.223G>A	p.Val75Met	missense	Exon 3 of 12	ENSP00000355126.1	Q8IUX8-1
	EGFL6	ENST00000380602.3	TSL:1	c.223G>A	p.Val75Met	missense	Exon 3 of 12	ENSP00000369976.3	Q8IUX8-2
	EGFL6	ENST00000857787.1		c.223G>A	p.Val75Met	missense	Exon 3 of 11	ENSP00000527846.1

Frequencies

GnomAD3 genomes AF: 0.00552 AC: 617 AN: 111786 Hom.: 4 Cov.: 23

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

GnomAD2 exomes AF: 0.00427 AC: 781 AN: 183011 AF XY: 0.00403

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 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

African (AFR) AF: 0.000606 AC: 16 AN: 26387

American (AMR) AF: 0.00179 AC: 63 AN: 35188

Ashkenazi Jewish (ASJ) AF: 0.00837 AC: 162 AN: 19353

East Asian (EAS) AF: 0.0000662 AC: 2 AN: 30189

South Asian (SAS) AF: 0.00109 AC: 59 AN: 53974

European-Finnish (FIN) AF: 0.00755 AC: 306 AN: 40510

Middle Eastern (MID) AF: 0.00194 AC: 8 AN: 4126

European-Non Finnish (NFE) AF: 0.00766 AC: 6444 AN: 841503

Other (OTH) AF: 0.00569 AC: 262 AN: 46065

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

African (AFR) AF: 0.00120 AC: 37 AN: 30761

American (AMR) AF: 0.00616 AC: 65 AN: 10546

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 32 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3575

South Asian (SAS) AF: 0.000748 AC: 2 AN: 2674

European-Finnish (FIN) AF: 0.00777 AC: 47 AN: 6046

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00795 AC: 423 AN: 53183

Other (OTH) AF: 0.00665 AC: 10 AN: 1503

Alfa AF: 0.00631 Hom.: 125

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

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0086	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.1
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.32
Sift	Benign	0.086	T
Sift4G	Benign	0.070	T
Polyphen		0.71	P
Vest4		0.15
MVP		0.74
MPC		0.79
ClinPred		0.012	T
GERP RS		4.1
Varity_R		0.13
gMVP		0.41
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs141324039; hg19: chrX-13612990;