NM_153702.4:c.378G>T

Variant names:

• chr4-140537520-G-T
• NM_153702.4:c.378G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153702.4(ELMOD2):​c.378G>T​(p.Gln126His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ELMOD2 NM_153702.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.445

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20824179).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELMOD2	NM_153702.4	c.378G>T	p.Gln126His	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.378G>T	p.Gln126His	missense_variant	Exon 5 of 9	1	NM_153702.4	ENSP00000326342.3
ELMOD2	ENST00000502397.5	c.378G>T	p.Gln126His	missense_variant	Exon 5 of 6	5		ENSP00000422582.1
ELMOD2	ENST00000513606.1	c.147G>T	p.Gln49His	missense_variant	Exon 4 of 5	4		ENSP00000427592.1
ELMOD2	ENST00000512057.1	n.523G>T		non_coding_transcript_exon_variant	Exon 2 of 5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445906 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 718696

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: 9.04e-7

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	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.5
DANN	Benign	0.87
DEOGEN2	Benign	0.040	T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.031
Sift	Uncertain	0.016	D;D;D
Sift4G	Uncertain	0.036	D;T;D
Polyphen		0.0030	B;.;.
Vest4		0.19
MutPred		0.43		Loss of stability (P = 0.1658);Loss of stability (P = 0.1658);.;
MVP		0.10
MPC		0.041
ClinPred		0.15	T
GERP RS		-9.3
Varity_R		0.061
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr4-141458674;