chrX-13603406-C-T

Position:

• chrX-13603406-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_015507.4(EGFL6):​c.490C>T​(p.Arg164Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,208,543 control chromosomes in the GnomAD database, including 66 homozygotes. There are 828 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.015 (33 hom., 437 hem., cov: 23)
  • Exomes 𝑓: 0.0015 (33 hom. 391 hem.)
• Consequence: EGFL6 NM_015507.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 7.35

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0047973096).
• BP6: Variant X-13603406-C-T is Benign according to our data. Variant chrX-13603406-C-T is described in ClinVar as [Benign]. Clinvar id is 712290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.015 (1680/112229) while in subpopulation AFR AF= 0.052 (1605/30884). AF 95% confidence interval is 0.0499. There are 33 homozygotes in gnomad4. There are 437 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 33 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFL6	NM_015507.4	c.490C>T	p.Arg164Cys	missense_variant	5/12	ENST00000361306.6
EGFL6	NM_001167890.2	c.490C>T	p.Arg164Cys	missense_variant	5/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFL6	ENST00000361306.6	c.490C>T	p.Arg164Cys	missense_variant	5/12	1	NM_015507.4	A2
EGFL6	ENST00000380602.3	c.490C>T	p.Arg164Cys	missense_variant	5/12	1		P4

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 1676 AN: 112174 Hom.: 33 Cov.: 23 AF XY: 0.0126 AC XY: 434 AN XY: 34348

Gnomad AFR AF: 0.0520

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000376

Gnomad OTH AF: 0.0132

GnomAD3 exomes AF: 0.00432 AC: 778 AN: 179967 Hom.: 16 AF XY: 0.00277 AC XY: 179 AN XY: 64545

Gnomad AFR exome AF: 0.0534

Gnomad AMR exome AF: 0.00271

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000495

Gnomad OTH exome AF: 0.00158

GnomAD4 exome AF: 0.00146 AC: 1605 AN: 1096314 Hom.: 33 Cov.: 30 AF XY: 0.00108 AC XY: 391 AN XY: 361780

Gnomad4 AFR exome AF: 0.0506

Gnomad4 AMR exome AF: 0.00306

Gnomad4 ASJ exome AF: 0.0000517

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000186

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000309

Gnomad4 OTH exome AF: 0.00289

GnomAD4 genome AF: 0.0150 AC: 1680 AN: 112229 Hom.: 33 Cov.: 23 AF XY: 0.0127 AC XY: 437 AN XY: 34413

Gnomad4 AFR AF: 0.0520

Gnomad4 AMR AF: 0.00498

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000376

Gnomad4 OTH AF: 0.0130

Alfa AF: 0.00212 Hom.: 74

Bravo AF: 0.0168

ESP6500AA AF: 0.0545 AC: 209

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00482 AC: 585

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.025	T;.
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.65	T;T
MetaRNN	Benign	0.0048	T;T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.5	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-4.3	D;D
REVEL	Uncertain	0.34
Sift	Benign	0.043	D;D
Sift4G	Uncertain	0.029	D;D
Polyphen		0.013	B;D
Vest4		0.17
MVP		0.70
MPC		0.33
ClinPred		0.036	T
GERP RS		5.1
Varity_R		0.22
gMVP		0.74

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

LitVar

Other links and lift over

dbSNP: rs34613284; hg19: chrX-13621525;