1-225514768-G-C

Variant names:

• chr1-225514768-G-C
• rs754063416
• NM_018212.6:c.1046C>G

Variant summary

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

The NM_018212.6(ENAH):​c.1046C>G​(p.Pro349Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P349L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: ENAH NM_018212.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.24
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3987656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENAH	NM_018212.6	c.1046C>G	p.Pro349Arg	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.1046C>G	p.Pro349Arg	missense_variant	Exon 7 of 14	1	NM_018212.6	ENSP00000355808.2

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome AF: 0.00000302 AC: 4 AN: 1325500 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 660416

African (AFR) AF: 0.00 AC: 0 AN: 28238

American (AMR) AF: 0.00 AC: 0 AN: 30790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23638

East Asian (EAS) AF: 0.00 AC: 0 AN: 33538

South Asian (SAS) AF: 0.00 AC: 0 AN: 76912

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3890

European-Non Finnish (NFE) AF: 0.00000391 AC: 4 AN: 1023040

Other (OTH) AF: 0.00 AC: 0 AN: 55208

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D;.;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.67	T;D;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Uncertain	0.63	D
MutationAssessor	Uncertain	2.7	M;.;M
PhyloP100		3.2
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-5.0	D;.;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.012	D;.;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.45
MutPred		0.30		Loss of glycosylation at P349 (P = 5e-04);.;Loss of glycosylation at P349 (P = 5e-04);
MVP		0.52
MPC		0.96
ClinPred		0.95	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.43
gMVP		0.29
Mutation Taster		=83/17	polymorphism

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: rs754063416; hg19: chr1-225702470;