chr7-36284690-C-T

Position:

• chr7-36284690-C-T

Variant summary

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

The NM_030636.3(EEPD1):​c.1046C>T​(p.Ala349Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EEPD1 NM_030636.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.33

Genes affected

EEPD1 (HGNC:22223): (endonuclease/exonuclease/phosphatase family domain containing 1) Predicted to enable DNA binding activity. Involved in positive regulation of cholesterol efflux. Is anchored component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.08114508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EEPD1	NM_030636.3	c.1046C>T	p.Ala349Val	missense_variant	5/8	ENST00000242108.9	NP_085139.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EEPD1	ENST00000242108.9	c.1046C>T	p.Ala349Val	missense_variant	5/8	1	NM_030636.3	ENSP00000242108	P1
EEPD1	ENST00000487069.5	n.148C>T		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2023

The c.1046C>T (p.A349V) alteration is located in exon 5 (coding exon 4) of the EEPD1 gene. This alteration results from a C to T substitution at nucleotide position 1046, causing the alanine (A) at amino acid position 349 to be replaced by a valine (V). 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	0.070
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	8.8
DANN	Benign	0.90
DEOGEN2	Benign	0.094	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.68	.;T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.081	T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	-0.32	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.35	N;N
REVEL	Benign	0.11
Sift	Benign	0.49	T;T
Sift4G	Benign	0.77	T;T
Polyphen		0.0	B;B
Vest4		0.076
MutPred		0.40		Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);
MVP		0.53
MPC		0.42
ClinPred		0.043	T
GERP RS		1.6
Varity_R		0.032
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr7-36324299;