rs775266200

Variant names:

• chrX-13594880-A-G
• rs775266200
• NM_015507.4:c.232A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-13594880-A-G
• chrX-13594880-A-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_015507.4(EGFL6):​c.232A>G​(p.Asn78Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,209,334 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.000012 (0 hom. 3 hem.)
• Consequence: EGFL6 NM_015507.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.08
• Publications: 1 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3427224).
• BS2: High Hemizygotes in GnomAdExome4 at 3 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.232A>G	p.Asn78Asp	missense	Exon 3 of 12	NP_056322.2
	EGFL6	NM_001167890.2		c.232A>G	p.Asn78Asp	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.232A>G	p.Asn78Asp	missense	Exon 3 of 12	ENSP00000355126.1	Q8IUX8-1
	EGFL6	ENST00000380602.3	TSL:1	c.232A>G	p.Asn78Asp	missense	Exon 3 of 12	ENSP00000369976.3	Q8IUX8-2
	EGFL6	ENST00000857787.1		c.232A>G	p.Asn78Asp	missense	Exon 3 of 11	ENSP00000527846.1

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111925 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000558

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000546 AC: 1 AN: 183010 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000723

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000118 AC: 13 AN: 1097409 Hom.: 0 Cov.: 29 AF XY: 0.00000827 AC XY: 3 AN XY: 362815

African (AFR) AF: 0.00 AC: 0 AN: 26393

American (AMR) AF: 0.00 AC: 0 AN: 35189

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19360

East Asian (EAS) AF: 0.000431 AC: 13 AN: 30193

South Asian (SAS) AF: 0.00 AC: 0 AN: 53980

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40499

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4124

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841618

Other (OTH) AF: 0.00 AC: 0 AN: 46053

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111925 Hom.: 0 Cov.: 22 AF XY: 0.0000293 AC XY: 1 AN XY: 34101

African (AFR) AF: 0.00 AC: 0 AN: 30726

American (AMR) AF: 0.00 AC: 0 AN: 10559

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.000558 AC: 2 AN: 3584

South Asian (SAS) AF: 0.00 AC: 0 AN: 2696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6077

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53220

Other (OTH) AF: 0.00 AC: 0 AN: 1492

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	0.070	N
PhyloP100		7.1
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.37
Sift	Benign	0.065	T
Sift4G	Benign	0.10	T
Polyphen		0.86	P
Vest4		0.50
MutPred		0.46		Gain of ubiquitination at K79 (P = 0.0483)
MVP		0.76
MPC		0.32
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.78
gMVP		0.70
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs775266200; hg19: chrX-13612999;