rs1234042385

Variant names:

• chr19-16425165-C-A
• rs1234042385
• NM_001258374.3:c.710G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-16425165-C-A
• chr19-16425165-C-G
• chr19-16425165-C-T

Variant summary

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

The NM_001258374.3(EPS15L1):​c.710G>T​(p.Arg237Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000705 in 1,417,502 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R237H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: EPS15L1 NM_001258374.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.70
• Publications: 0 publications found

Genes affected

EPS15L1 (HGNC:24634): (epidermal growth factor receptor pathway substrate 15 like 1) Enables cadherin binding activity. Predicted to be involved in endocytosis and endosomal transport. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

EPS15L1 Gene-Disease associations (from GenCC):

• split hand-foot malformation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
EPS15L1	NM_001258374.3	c.710G>T	p.Arg237Leu	missense_variant	Exon 9 of 24	ENST00000455140.7	NP_001245303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPS15L1	ENST00000455140.7	c.710G>T	p.Arg237Leu	missense_variant	Exon 9 of 24	2	NM_001258374.3	ENSP00000393313.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1417502 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 704626

African (AFR) AF: 0.00 AC: 0 AN: 32066

American (AMR) AF: 0.00 AC: 0 AN: 43184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24262

East Asian (EAS) AF: 0.00 AC: 0 AN: 36224

South Asian (SAS) AF: 0.00 AC: 0 AN: 85800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49766

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5558

European-Non Finnish (NFE) AF: 9.23e-7 AC: 1 AN: 1083330

Other (OTH) AF: 0.00 AC: 0 AN: 57312

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	.;T;.;T;.;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.44	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M;M;.;.;M
PhyloP100		4.7
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.5	D;N;N;.;.;.
REVEL	Benign	0.17
Sift	Benign	0.16	T;T;T;.;.;.
Sift4G	Benign	0.063	T;T;D;D;D;D
Polyphen		0.98	.;D;.;.;.;.
Vest4		0.78
MutPred		0.32		Loss of solvent accessibility (P = 0.001);Loss of solvent accessibility (P = 0.001);Loss of solvent accessibility (P = 0.001);Loss of solvent accessibility (P = 0.001);.;Loss of solvent accessibility (P = 0.001);
MVP		0.31
MPC		1.4
ClinPred		0.96	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.28
gMVP		0.58
Mutation Taster		=22/78	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: rs1234042385; hg19: chr19-16535976;