X-13603406-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

1
6
9

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.35
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
EGFL6NM_015507.4 linkuse as main transcriptc.490C>T p.Arg164Cys missense_variant 5/12 ENST00000361306.6
EGFL6NM_001167890.2 linkuse as main transcriptc.490C>T p.Arg164Cys missense_variant 5/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EGFL6ENST00000361306.6 linkuse as main transcriptc.490C>T p.Arg164Cys missense_variant 5/121 NM_015507.4 A2Q8IUX8-1
EGFL6ENST00000380602.3 linkuse as main transcriptc.490C>T p.Arg164Cys missense_variant 5/121 P4Q8IUX8-2

Frequencies

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

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMay 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34613284; hg19: chrX-13621525; API