19-11513956-C-A

Variant names:

• chr19-11513956-C-A
• rs755089384
• NM_016581.5:c.362G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_016581.5(ECSIT):​c.362G>T​(p.Gly121Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G121D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ECSIT NM_016581.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.39
• Publications: 1 publications found

Genes affected

ECSIT (HGNC:29548): (ECSIT signaling integrator) Predicted to enable DNA-binding transcription factor activity and chromatin binding activity. Involved in regulation of oxidoreductase activity and regulation of protein complex stability. Located in cytosol; mitochondrion; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.984

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016581.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECSIT	NM_016581.5	MANE Select	c.362G>T	p.Gly121Val	missense	Exon 3 of 8	NP_057665.2
	ECSIT	NM_001142464.3		c.362G>T	p.Gly121Val	missense	Exon 3 of 7	NP_001135936.1	Q9BQ95-2
	ECSIT	NM_001243204.2		c.362G>T	p.Gly121Val	missense	Exon 3 of 8	NP_001230133.1	Q9BQ95-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECSIT	ENST00000270517.12	TSL:1 MANE Select	c.362G>T	p.Gly121Val	missense	Exon 3 of 8	ENSP00000270517.6	Q9BQ95-1
	ECSIT	ENST00000252440.11	TSL:1	c.362G>T	p.Gly121Val	missense	Exon 3 of 7	ENSP00000252440.6	Q9BQ95-2
	ECSIT	ENST00000591104.5	TSL:1	c.362G>T	p.Gly121Val	missense	Exon 3 of 8	ENSP00000466559.1	Q9BQ95-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	D
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.35	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.67	D
MutationAssessor	Pathogenic	3.5	M
PhyloP100		7.4
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-8.7	D
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.90		Loss of catalytic residue at V122 (P = 0.0632)
MVP		0.94
MPC		1.1
ClinPred		1.0	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.94
gMVP		0.79
Mutation Taster		=5/95	disease causing

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

Other links and lift over

dbSNP: rs755089384; hg19: chr19-11624771;