5-38370329-T-A

Position:

• chr5-38370329-T-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_152403.4(EGFLAM):​c.579T>A​(p.His193Gln) 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 benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EGFLAM NM_152403.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.57

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031907022).
• BP6: Variant 5-38370329-T-A is Benign according to our data. Variant chr5-38370329-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 3274749.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFLAM	NM_152403.4	c.579T>A	p.His193Gln	missense_variant	6/22	ENST00000322350.10	NP_689616.2
EGFLAM	NM_001205301.2	c.579T>A	p.His193Gln	missense_variant	6/23		NP_001192230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFLAM	ENST00000322350.10	c.579T>A	p.His193Gln	missense_variant	6/22	1	NM_152403.4	ENSP00000313084	P3
EGFLAM	ENST00000354891.7	c.579T>A	p.His193Gln	missense_variant	6/23	1		ENSP00000346964	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.72
DEOGEN2	Benign	0.043	T;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.032	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.76	N;N
MutationTaster	Benign	0.98	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.030	N;N
REVEL	Benign	0.032
Sift	Benign	0.91	T;T
Sift4G	Benign	0.48	T;T
Polyphen		0.0	B;B
Vest4		0.035
MutPred		0.29		Gain of MoRF binding (P = 0.1365);Gain of MoRF binding (P = 0.1365);
MVP		0.12
MPC		0.092
ClinPred		0.078	T
GERP RS		2.1
Varity_R		0.14
gMVP		0.31

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: chr5-38370431;