1-225514778-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENAH	NM_018212.6	c.1036G>T	p.Gly346Trp	missense_variant	Exon 7 of 14	ENST00000366843.7	NP_060682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENAH	ENST00000366843.7	c.1036G>T	p.Gly346Trp	missense_variant	Exon 7 of 14	1	NM_018212.6	ENSP00000355808.2

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000140

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1036G>T (p.G346W) alteration is located in exon 7 (coding exon 7) of the ENAH gene. This alteration results from a G to T substitution at nucleotide position 1036, causing the glycine (G) at amino acid position 346 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;D;T
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.45	T;T;T
MetaSVM	Uncertain	0.66	D
MutationAssessor	Uncertain	2.7	M;.;M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-4.4	D;.;D
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D;.;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.69
MutPred		0.19		Loss of relative solvent accessibility (P = 0.0186);.;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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-225702480;