5-38406218-G-T

Position:

• chr5-38406218-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152403.4(EGFLAM):​c.805G>T​(p.Asp269Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EGFLAM NM_152403.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.44

Genes affected

EGFLAM (HGNC:26810): (EGF like, fibronectin type III and laminin G domains) Predicted to enable calcium ion binding activity and glycosaminoglycan binding activity. Predicted to be involved in animal organ morphogenesis and tissue development. Predicted to act upstream of or within extracellular matrix organization; peptide cross-linking via chondroitin 4-sulfate glycosaminoglycan; and positive regulation of cell-substrate adhesion. Part of cell surface. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.748

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFLAM	NM_152403.4	c.805G>T	p.Asp269Tyr	missense_variant	7/22	ENST00000322350.10	NP_689616.2
EGFLAM	NM_001205301.2	c.805G>T	p.Asp269Tyr	missense_variant	7/23		NP_001192230.1
EGFLAM	NM_182798.3	c.103G>T	p.Asp35Tyr	missense_variant	2/17		NP_877950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFLAM	ENST00000322350.10	c.805G>T	p.Asp269Tyr	missense_variant	7/22	1	NM_152403.4	ENSP00000313084	P3
EGFLAM	ENST00000354891.7	c.805G>T	p.Asp269Tyr	missense_variant	7/23	1		ENSP00000346964	A2
EGFLAM	ENST00000397202.6	c.-364+2327G>T		intron_variant		1		ENSP00000380385
EGFLAM	ENST00000336740.10	c.103G>T	p.Asp35Tyr	missense_variant	2/17	2		ENSP00000337607

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 18, 2022

The c.805G>T (p.D269Y) alteration is located in exon 7 (coding exon 7) of the EGFLAM gene. This alteration results from a G to T substitution at nucleotide position 805, causing the aspartic acid (D) at amino acid position 269 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T;.;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.75	D;D;D
MetaSVM	Uncertain	0.50	D
MutationAssessor	Uncertain	2.5	M;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Uncertain	0.44
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.76
MutPred		0.41		Gain of phosphorylation at D269 (P = 0.0014);Gain of phosphorylation at D269 (P = 0.0014);.;
MVP		0.89
MPC		0.51
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.36
gMVP		0.85

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-38406320;