Genetic Variant EGFLAM:c.-44C>T (chr5-38427057-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000397202.6(EGFLAM):c.-44C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000041 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

EGFLAM
ENST00000397202.6 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

Publications

0 publications found

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:

EGFLAM-AS1 (HGNC:41169): (EGFLAM antisense RNA 1)

EGFLAM-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397202.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EGFLAM	NM_152403.4	MANE Select	c.1859C>T	p.Ala620Val	missense	Exon 14 of 22	NP_689616.2
EGFLAM	NM_001205301.2		c.1859C>T	p.Ala620Val	missense	Exon 14 of 23	NP_001192230.1	Q63HQ2-1
EGFLAM	NM_182798.3		c.1157C>T	p.Ala386Val	missense	Exon 9 of 17	NP_877950.1	Q63HQ2-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EGFLAM	ENST00000397202.6	TSL:1	c.-44C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 12	ENSP00000380385.2	Q63HQ2-3
EGFLAM	ENST00000322350.10	TSL:1 MANE Select	c.1859C>T	p.Ala620Val	missense	Exon 14 of 22	ENSP00000313084.5	Q63HQ2-2
EGFLAM	ENST00000354891.7	TSL:1	c.1859C>T	p.Ala620Val	missense	Exon 14 of 23	ENSP00000346964.3	Q63HQ2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251354

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111998

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Uncertain

0.073

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.038

MetaRNN

Uncertain

0.74

MetaSVM

Benign

-0.36

MutationAssessor

Benign

1.8

PhyloP100

5.7

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.54

REVEL

Benign

0.21

Sift

Benign

0.056

Sift4G

Uncertain

0.0070

Polyphen

0.99

Vest4

0.78

MutPred

0.34

Loss of catalytic residue at A620 (P = 0.1236)

MVP

0.76

MPC

0.48

ClinPred

0.70

GERP RS

5.9

Varity_R

0.14

gMVP

0.59

Mutation Taster

=125/175

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over