rs770767653

Variant names:

• chr1-225514813-G-A
• rs770767653
• NM_018212.6:c.1001C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-225514813-G-A
• chr1-225514813-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_018212.6(ENAH):​c.1001C>T​(p.Pro334Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,559,452 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 24)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: ENAH NM_018212.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.92
• 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 -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENAH	NM_018212.6	c.1001C>T	p.Pro334Leu	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.1001C>T	p.Pro334Leu	missense_variant	Exon 7 of 14	1	NM_018212.6	ENSP00000355808.2

Frequencies

GnomAD3 genomes AF: 0.0000134 AC: 2 AN: 149514 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000297

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000161 AC: 3 AN: 186566 AF XY: 0.0000195

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000199 AC: 28 AN: 1409938 Hom.: 0 Cov.: 30 AF XY: 0.0000228 AC XY: 16 AN XY: 700404

African (AFR) AF: 0.00 AC: 0 AN: 30864

American (AMR) AF: 0.00 AC: 0 AN: 32840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24314

East Asian (EAS) AF: 0.00 AC: 0 AN: 37830

South Asian (SAS) AF: 0.0000254 AC: 2 AN: 78816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51940

Middle Eastern (MID) AF: 0.000435 AC: 2 AN: 4598

European-Non Finnish (NFE) AF: 0.0000193 AC: 21 AN: 1090528

Other (OTH) AF: 0.0000515 AC: 3 AN: 58208

GnomAD4 genome AF: 0.0000134 AC: 2 AN: 149514 Hom.: 0 Cov.: 24 AF XY: 0.0000274 AC XY: 2 AN XY: 72954

African (AFR) AF: 0.00 AC: 0 AN: 40454

American (AMR) AF: 0.00 AC: 0 AN: 14992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3434

East Asian (EAS) AF: 0.00 AC: 0 AN: 5068

South Asian (SAS) AF: 0.00 AC: 0 AN: 4644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000297 AC: 2 AN: 67276

Other (OTH) AF: 0.00 AC: 0 AN: 2034

Alfa AF: 0.0000843 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 15, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1001C>T (p.P334L) alteration is located in exon 7 (coding exon 7) of the ENAH gene. This alteration results from a C to T substitution at nucleotide position 1001, causing the proline (P) at amino acid position 334 to be replaced by a leucine (L). 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	0.092
BayesDel_addAF	Benign	-0.0079	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D;.;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Pathogenic	0.37	D
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Uncertain	0.24	D
MutationAssessor	Uncertain	2.8	M;.;M
PhyloP100		4.9
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.8	D;.;D
REVEL	Uncertain	0.40
Sift	Benign	0.40	T;.;T
Sift4G	Uncertain	0.0070	D;T;D
Polyphen		1.0	D;.;D
Vest4		0.50
MutPred		0.31		Loss of glycosylation at P334 (P = 0.0012);.;Loss of glycosylation at P334 (P = 0.0012);
MVP		0.83
MPC		0.95
ClinPred		0.97	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.080
gMVP		0.14
Mutation Taster		=63/37	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: rs770767653; hg19: chr1-225702515;