NM_018212.6:c.1036G>T

Variant names:

• chr1-225514778-C-A
• rs778983588
• NM_018212.6:c.1036G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018212.6(ENAH):​c.1036G>T​(p.Gly346Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000117 in 855,296 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: ENAH NM_018212.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1036G>T	p.Gly346Trp	missense	Exon 7 of 14	NP_060682.2
	ENAH	NM_001420159.1		c.1777G>T	p.Gly593Trp	missense	Exon 8 of 16	NP_001407088.1
	ENAH	NM_001420160.1		c.1720G>T	p.Gly574Trp	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.1036G>T	p.Gly346Trp	missense	Exon 7 of 14	ENSP00000355808.2	Q8N8S7-2
	ENAH	ENST00000366844.7	TSL:1	c.1036G>T	p.Gly346Trp	missense	Exon 7 of 15	ENSP00000355809.2	Q8N8S7-1
	ENAH	ENST00000893225.1		c.1720G>T	p.Gly574Trp	missense	Exon 7 of 15	ENSP00000563284.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000117 AC: 1 AN: 855296 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 415160

African (AFR) AF: 0.00 AC: 0 AN: 16670

American (AMR) AF: 0.00 AC: 0 AN: 15060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11158

East Asian (EAS) AF: 0.00 AC: 0 AN: 8630

South Asian (SAS) AF: 0.00 AC: 0 AN: 34276

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22744

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1976

European-Non Finnish (NFE) AF: 0.00000140 AC: 1 AN: 715152

Other (OTH) AF: 0.00 AC: 0 AN: 29630

GnomAD4 genome Cov.: 0

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	Uncertain	0.51
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.67	D
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Uncertain	0.66	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.6
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.69
MutPred		0.19		Loss of relative solvent accessibility (P = 0.0186)
MVP		0.48
MPC		1.0
ClinPred		0.99	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.63
gMVP		0.18
Mutation Taster		=17/83	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: rs778983588; hg19: chr1-225702480;