X-13600042-C-T

Variant names:

• chrX-13600042-C-T
• rs16999038
• NM_015507.4:c.348C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_015507.4(EGFL6):​c.348C>T​(p.Tyr116Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00215 in 1,209,547 control chromosomes in the GnomAD database, including 33 homozygotes. There are 703 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (19 hom., 335 hem., cov: 22)
  • Exomes 𝑓: 0.0012 (14 hom. 368 hem.)
• Consequence: EGFL6 NM_015507.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.64
• 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant X-13600042-C-T is Benign according to our data. Variant chrX-13600042-C-T is described in ClinVar as Benign. ClinVar VariationId is 777786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.64 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0111 (1242/111849) while in subpopulation AFR AF = 0.038 (1170/30801). AF 95% confidence interval is 0.0362. There are 19 homozygotes in GnomAd4. There are 335 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 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.348C>T	p.Tyr116Tyr	synonymous	Exon 4 of 12	NP_056322.2
	EGFL6	NM_001167890.2		c.348C>T	p.Tyr116Tyr	synonymous	Exon 4 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.348C>T	p.Tyr116Tyr	synonymous	Exon 4 of 12	ENSP00000355126.1	Q8IUX8-1
	EGFL6	ENST00000380602.3	TSL:1	c.348C>T	p.Tyr116Tyr	synonymous	Exon 4 of 12	ENSP00000369976.3	Q8IUX8-2
	EGFL6	ENST00000857787.1		c.348C>T	p.Tyr116Tyr	synonymous	Exon 4 of 11	ENSP00000527846.1

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1243 AN: 111796 Hom.: 19 Cov.: 22

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00476

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: 0.000113

Gnomad OTH AF: 0.0107

GnomAD2 exomes AF: 0.00320 AC: 586 AN: 183013 AF XY: 0.00212

Gnomad AFR exome AF: 0.0405

Gnomad AMR exome AF: 0.00135

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000110

Gnomad OTH exome AF: 0.00155

GnomAD4 exome AF: 0.00124 AC: 1356 AN: 1097698 Hom.: 14 Cov.: 30 AF XY: 0.00101 AC XY: 368 AN XY: 363056

African (AFR) AF: 0.0432 AC: 1138 AN: 26373

American (AMR) AF: 0.00188 AC: 66 AN: 35199

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19376

East Asian (EAS) AF: 0.00 AC: 0 AN: 30193

South Asian (SAS) AF: 0.000129 AC: 7 AN: 54117

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40511

Middle Eastern (MID) AF: 0.000967 AC: 4 AN: 4136

European-Non Finnish (NFE) AF: 0.0000297 AC: 25 AN: 841715

Other (OTH) AF: 0.00252 AC: 116 AN: 46078

GnomAD4 genome AF: 0.0111 AC: 1242 AN: 111849 Hom.: 19 Cov.: 22 AF XY: 0.00984 AC XY: 335 AN XY: 34031

African (AFR) AF: 0.0380 AC: 1170 AN: 30801

American (AMR) AF: 0.00475 AC: 50 AN: 10526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3561

South Asian (SAS) AF: 0.00 AC: 0 AN: 2683

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6039

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

European-Non Finnish (NFE) AF: 0.000113 AC: 6 AN: 53174

Other (OTH) AF: 0.0105 AC: 16 AN: 1520

Alfa AF: 0.00497 Hom.: 31

Bravo AF: 0.0133

EpiCase AF: 0.00

EpiControl AF: 0.0000594

ClinVar

ClinVar submissions

Significance: 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
BayesDel_noAF	Benign	-0.39
CADD	Benign	6.7
DANN	Benign	0.79
PhyloP100		2.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs16999038; hg19: chrX-13618161;