Variant 5-38407099-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152403.4(EGFLAM):c.1100C>T(p.Ser367Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000607 in 1,614,014 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000064 ( 1 hom. )

Consequence

EGFLAM
NM_152403.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.48

Variant links:

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]

EGFLAM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EGFLAM	NM_152403.4 linkuse as main transcript	c.1100C>T	p.Ser367Leu	missense_variant	8/22	ENST00000322350.10
EGFLAM	NM_001205301.2 linkuse as main transcript	c.1100C>T	p.Ser367Leu	missense_variant	8/23
EGFLAM	NM_182798.3 linkuse as main transcript	c.398C>T	p.Ser133Leu	missense_variant	3/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFLAM	ENST00000322350.10 linkuse as main transcript	c.1100C>T	p.Ser367Leu	missense_variant	8/22	1	NM_152403.4	P3	Q63HQ2-2
EGFLAM	ENST00000354891.7 linkuse as main transcript	c.1100C>T	p.Ser367Leu	missense_variant	8/23	1		A2	Q63HQ2-1
EGFLAM	ENST00000397202.6 linkuse as main transcript	c.-364+3208C>T		intron_variant		1			Q63HQ2-3
EGFLAM	ENST00000336740.10 linkuse as main transcript	c.398C>T	p.Ser133Leu	missense_variant	3/17	2			Q63HQ2-4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000104

AC:

AN:

249392

Hom.:

AF XY:

0.0000741

AC XY:

AN XY:

134946

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000536

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.0000643

AC:

AN:

1461794

Hom.:

Cov.:

AF XY:

0.0000688

AC XY:

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000495

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000767

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2023

The c.1100C>T (p.S367L) alteration is located in exon 8 (coding exon 8) of the EGFLAM gene. This alteration results from a C to T substitution at nucleotide position 1100, causing the serine (S) at amino acid position 367 to be replaced by a leucine (L). 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

0.19

BayesDel_addAF

Benign

0.0020

BayesDel_noAF

Uncertain

0.070

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.20

T;.;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.68

D;D;D

MetaSVM

Uncertain

-0.033

MutationAssessor

Uncertain

2.8

M;M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.2

N;N;N

REVEL

Uncertain

0.47

Sift

Benign

0.12

T;T;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.77

MutPred

0.58

Loss of catalytic residue at S367 (P = 0.0862);Loss of catalytic residue at S367 (P = 0.0862);.;

MVP

0.86

MPC

0.33

ClinPred

0.73

GERP RS

4.8

Varity_R

0.13

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over