rs752934730

Variant names:

• chr19-11514017-C-T
• rs752934730
• NM_016581.5:c.301G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016581.5(ECSIT):​c.301G>A​(p.Val101Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,882 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: not found (cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: ECSIT NM_016581.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.243
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.79

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.301G>A	p.Val101Met	missense	Exon 3 of 8	NP_057665.2
	ECSIT	NM_001142464.3		c.301G>A	p.Val101Met	missense	Exon 3 of 7	NP_001135936.1	Q9BQ95-2
	ECSIT	NM_001243204.2		c.301G>A	p.Val101Met	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.301G>A	p.Val101Met	missense	Exon 3 of 8	ENSP00000270517.6	Q9BQ95-1
	ECSIT	ENST00000252440.11	TSL:1	c.301G>A	p.Val101Met	missense	Exon 3 of 7	ENSP00000252440.6	Q9BQ95-2
	ECSIT	ENST00000591104.5	TSL:1	c.301G>A	p.Val101Met	missense	Exon 3 of 8	ENSP00000466559.1	Q9BQ95-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251440 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1461882 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	Benign	0.19
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		0.24
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.53
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.33
MutPred		0.79		Gain of disorder (P = 0.0844)
MVP		0.64
MPC		0.72
ClinPred		0.95	D
GERP RS		3.3
Varity_R		0.059
gMVP		0.35
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs752934730; hg19: chr19-11624832;