1-225517199-G-C

Variant names:

• chr1-225517199-G-C
• NM_018212.6:c.910C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018212.6(ENAH):​c.910C>G​(p.Gln304Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENAH NM_018212.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.00

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21994433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENAH	NM_018212.6	c.910C>G	p.Gln304Glu	missense_variant	Exon 6 of 14	ENST00000366843.7	NP_060682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENAH	ENST00000366843.7	c.910C>G	p.Gln304Glu	missense_variant	Exon 6 of 14	1	NM_018212.6	ENSP00000355808.2
ENAH	ENST00000366844.7	c.910C>G	p.Gln304Glu	missense_variant	Exon 6 of 15	1		ENSP00000355809.2
ENAH	ENST00000635051.1	c.1606C>G	p.Gln536Glu	missense_variant	Exon 7 of 15	5		ENSP00000489607.1
ENAH	ENST00000696609.1	c.1228C>G	p.Gln410Glu	missense_variant	Exon 3 of 12			ENSP00000512753.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 18, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.910C>G (p.Q304E) alteration is located in exon 6 (coding exon 6) of the ENAH gene. This alteration results from a C to G substitution at nucleotide position 910, causing the glutamine (Q) at amino acid position 304 to be replaced by a glutamic acid (E). 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	Benign	0.080
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.;.
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.80	T;D;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Benign	1.4	L;.;L
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.99	N;.;N
REVEL	Benign	0.11
Sift	Benign	0.064	T;.;T
Sift4G	Benign	0.36	T;T;T
Polyphen		0.86	P;.;B
Vest4		0.36
MutPred		0.056		Gain of phosphorylation at S302 (P = 0.12);.;Gain of phosphorylation at S302 (P = 0.12);
MVP		0.33
MPC		0.87
ClinPred		0.81	D
GERP RS		5.3
Varity_R		0.13
gMVP		0.19

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: chr1-225704901;