1-225514759-G-A

Variant names:

• chr1-225514759-G-A
• rs866765514
• NM_018212.6:c.1055C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_018212.6(ENAH):​c.1055C>T​(p.Pro352Leu) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: ENAH NM_018212.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.63
• Publications: 1 publications found

Genes affected

ENAH (HGNC:18271): (ENAH actin regulator) This gene encodes a member of the enabled/ vasodilator-stimulated phosphoprotein. Members of this gene family are involved in actin-based motility. This protein is involved in regulating the assembly of actin filaments and modulates cell adhesion and motility. Alternate splice variants of this gene have been correlated with tumor invasiveness in certain tissues and these variants may serve as prognostic markers. A pseudogene of this gene is found on chromosome 3. [provided by RefSeq, Sep 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3521338).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018212.6. 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
	ENAH	NM_018212.6	MANE Select	c.1055C>T	p.Pro352Leu	missense	Exon 7 of 14	NP_060682.2
	ENAH	NM_001420159.1		c.1796C>T	p.Pro599Leu	missense	Exon 8 of 16	NP_001407088.1
	ENAH	NM_001420160.1		c.1739C>T	p.Pro580Leu	missense	Exon 7 of 15	NP_001407089.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENAH	ENST00000366843.7	TSL:1 MANE Select	c.1055C>T	p.Pro352Leu	missense	Exon 7 of 14	ENSP00000355808.2	Q8N8S7-2
	ENAH	ENST00000366844.7	TSL:1	c.1055C>T	p.Pro352Leu	missense	Exon 7 of 15	ENSP00000355809.2	Q8N8S7-1
	ENAH	ENST00000893225.1		c.1739C>T	p.Pro580Leu	missense	Exon 7 of 15	ENSP00000563284.1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome AF: 0.00000236 AC: 3 AN: 1272540 Hom.: 0 Cov.: 20 AF XY: 0.00000314 AC XY: 2 AN XY: 636338

African (AFR) AF: 0.00 AC: 0 AN: 26420

American (AMR) AF: 0.00 AC: 0 AN: 28482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21618

East Asian (EAS) AF: 0.00 AC: 0 AN: 31742

South Asian (SAS) AF: 0.00 AC: 0 AN: 76278

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3674

European-Non Finnish (NFE) AF: 0.00000305 AC: 3 AN: 983304

Other (OTH) AF: 0.00 AC: 0 AN: 51902

GnomAD4 genome Cov.: 19

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	0.11
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.29	D
MetaRNN	Benign	0.35	T
MetaSVM	Uncertain	0.35	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.6
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.48
MutPred		0.35		Loss of glycosylation at P352 (P = 1e-04)
MVP		0.56
MPC		0.95
ClinPred		0.99	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.52
gMVP		0.19
Mutation Taster		=37/63	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: rs866765514; hg19: chr1-225702461;