NM_016581.5:c.689G>A

Variant names:

• chr19-11513105-C-T
• rs1242419382
• NM_016581.5:c.689G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016581.5(ECSIT):​c.689G>A​(p.Gly230Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: ECSIT NM_016581.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.28
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.914

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.689G>A	p.Gly230Asp	missense	Exon 4 of 8	NP_057665.2
	ECSIT	NM_001142464.3		c.689G>A	p.Gly230Asp	missense	Exon 4 of 7	NP_001135936.1	Q9BQ95-2
	ECSIT	NM_001243204.2		c.689G>A	p.Gly230Asp	missense	Exon 4 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.689G>A	p.Gly230Asp	missense	Exon 4 of 8	ENSP00000270517.6	Q9BQ95-1
	ECSIT	ENST00000252440.11	TSL:1	c.689G>A	p.Gly230Asp	missense	Exon 4 of 7	ENSP00000252440.6	Q9BQ95-2
	ECSIT	ENST00000591104.5	TSL:1	c.689G>A	p.Gly230Asp	missense	Exon 4 of 8	ENSP00000466559.1	Q9BQ95-4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152200 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152200 Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1 AN XY: 74360

African (AFR) AF: 0.0000241 AC: 1 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D
Eigen	Benign	-0.051
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.3
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.052	T
Polyphen		0.97	D
Vest4		0.75
MutPred		0.78		Gain of disorder (P = 0.0565)
MVP		0.59
MPC		1.0
ClinPred		0.96	D
GERP RS		1.4
Varity_R		0.28
gMVP		0.84
Mutation Taster		=86/14	polymorphism

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: rs1242419382; hg19: chr19-11623920;