chr19-11513956-C-A

Variant names:

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

Variant summary

Our verdict is Likely pathogenic. Variant got 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

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

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECSIT	NM_016581.5	c.362G>T	p.Gly121Val	missense_variant	Exon 3 of 8	ENST00000270517.12	NP_057665.2
ECSIT	NM_001142464.3	c.362G>T	p.Gly121Val	missense_variant	Exon 3 of 7		NP_001135936.1
ECSIT	NM_001243204.2	c.362G>T	p.Gly121Val	missense_variant	Exon 3 of 8		NP_001230133.1
ECSIT	NM_001142465.3	c.96+5119G>T		intron_variant	Intron 2 of 5		NP_001135937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECSIT	ENST00000270517.12	c.362G>T	p.Gly121Val	missense_variant	Exon 3 of 8	1	NM_016581.5	ENSP00000270517.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;.;.;.;T;T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D;D;D;D;D;D;D
M_CAP	Pathogenic	0.35	D
MetaRNN	Pathogenic	0.98	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.67	D
MutationAssessor	Pathogenic	3.5	M;M;M;.;.;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-8.7	D;D;.;.;.;.;.
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0010	D;D;.;.;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;D;.;.;.
Polyphen		1.0	D;D;.;.;.;.;.
Vest4		0.84
MutPred		0.90		Loss of catalytic residue at V122 (P = 0.0632);Loss of catalytic residue at V122 (P = 0.0632);Loss of catalytic residue at V122 (P = 0.0632);.;.;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

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

LitVar

Other links and lift over

dbSNP: rs755089384; hg19: chr19-11624771;