NM_015507.4:c.307C>T

Variant names:

• chrX-13600001-C-T
• rs34109887
• NM_015507.4:c.307C>T

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.307C>T​(p.Arg103Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000346 in 1,208,487 control chromosomes in the GnomAD database, including 3 homozygotes. There are 114 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., 62 hem., cov: 22)
  • Exomes 𝑓: 0.00019 (2 hom. 52 hem.)
• Consequence: EGFL6 NM_015507.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.02
• Publications: 0 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=0.012380391).
• BP6: Variant X-13600001-C-T is Benign according to our data. Variant chrX-13600001-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 711786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd4 at 62 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.307C>T	p.Arg103Trp	missense	Exon 4 of 12	NP_056322.2
	EGFL6	NM_001167890.2		c.307C>T	p.Arg103Trp	missense	Exon 4 of 12	NP_001161362.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFL6	ENST00000361306.6	TSL:1 MANE Select	c.307C>T	p.Arg103Trp	missense	Exon 4 of 12	ENSP00000355126.1
	EGFL6	ENST00000380602.3	TSL:1	c.307C>T	p.Arg103Trp	missense	Exon 4 of 12	ENSP00000369976.3
	EGFL6	ENST00000857787.1		c.307C>T	p.Arg103Trp	missense	Exon 4 of 11	ENSP00000527846.1

Frequencies

GnomAD3 genomes AF: 0.00190 AC: 212 AN: 111620 Hom.: 1 Cov.: 22

Gnomad AFR AF: 0.00656

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000573

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: 0.00

Gnomad OTH AF: 0.00333

GnomAD2 exomes AF: 0.000547 AC: 100 AN: 182840 AF XY: 0.000253

Gnomad AFR exome AF: 0.00672

Gnomad AMR exome AF: 0.000403

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000188 AC: 206 AN: 1096814 Hom.: 2 Cov.: 29 AF XY: 0.000144 AC XY: 52 AN XY: 362196

African (AFR) AF: 0.00668 AC: 176 AN: 26350

American (AMR) AF: 0.000398 AC: 14 AN: 35188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19369

East Asian (EAS) AF: 0.00 AC: 0 AN: 30188

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54073

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40517

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 840944

Other (OTH) AF: 0.000282 AC: 13 AN: 46055

GnomAD4 genome AF: 0.00190 AC: 212 AN: 111673 Hom.: 1 Cov.: 22 AF XY: 0.00183 AC XY: 62 AN XY: 33849

African (AFR) AF: 0.00654 AC: 201 AN: 30713

American (AMR) AF: 0.000573 AC: 6 AN: 10477

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.00 AC: 0 AN: 3551

South Asian (SAS) AF: 0.00 AC: 0 AN: 2673

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53138

Other (OTH) AF: 0.00329 AC: 5 AN: 1519

Alfa AF: 0.000296 Hom.: 16

Bravo AF: 0.00210

ESP6500AA AF: 0.00600 AC: 23

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000667 AC: 81

ClinVar

ClinVar submissions as Germline

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	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.43	D
MetaRNN	Benign	0.012	T
MetaSVM	Uncertain	0.63	D
MutationAssessor	Benign	1.5	L
PhyloP100		4.0
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-7.6	D
REVEL	Uncertain	0.60
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.43
MVP		0.53
MPC		0.89
ClinPred		0.18	T
GERP RS		4.2
Varity_R		0.83
gMVP		0.74
Mutation Taster		=93/7	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: rs34109887; hg19: chrX-13618120;