chr4-140537441-T-A

Variant names:

• chr4-140537441-T-A
• NM_153702.4:c.299T>A

Variant summary

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

The NM_153702.4(ELMOD2):​c.299T>A​(p.Leu100Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,402,738 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ELMOD2 NM_153702.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.54

Genes affected

ELMOD2 (HGNC:28111): (ELMO domain containing 2) This gene encodes one of six engulfment and motility (ELMO) domain-containing proteins. This gene is thought to play a role in antiviral responses. Mutations in this gene may be involved in the cause of familial idiopathic pulmonary fibrosis. [provided by RefSeq, Sep 2010]

ACMG classification

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 rank	MANE	Protein	UniProt
ELMOD2	NM_153702.4	c.299T>A	p.Leu100Gln	missense_variant	Exon 5 of 9	ENST00000323570.8	NP_714913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELMOD2	ENST00000323570.8	c.299T>A	p.Leu100Gln	missense_variant	Exon 5 of 9	1	NM_153702.4	ENSP00000326342.3
ELMOD2	ENST00000502397.5	c.299T>A	p.Leu100Gln	missense_variant	Exon 5 of 6	5		ENSP00000422582.1
ELMOD2	ENST00000513606.1	c.68T>A	p.Leu23Gln	missense_variant	Exon 4 of 5	4		ENSP00000427592.1
ELMOD2	ENST00000512057.1	n.444T>A		non_coding_transcript_exon_variant	Exon 2 of 5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1402738 Hom.: 0 Cov.: 30 AF XY: 0.00000287 AC XY: 2 AN XY: 695952

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000275

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	T;T;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.5	M;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Uncertain	0.49
Sift	Benign	0.17	T;D;T
Sift4G	Benign	0.53	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.86
MutPred		0.51		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);.;
MVP		0.35
MPC		0.30
ClinPred		0.94	D
GERP RS		5.7
Varity_R		0.36
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr4-141458595;