chr7-36154494-C-T

Position:

• chr7-36154494-C-T

Variant summary

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

The NM_030636.3(EEPD1):​c.170C>T​(p.Thr57Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EEPD1 NM_030636.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.54

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EEPD1	NM_030636.3	c.170C>T	p.Thr57Met	missense_variant	2/8	ENST00000242108.9	NP_085139.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EEPD1	ENST00000242108.9	c.170C>T	p.Thr57Met	missense_variant	2/8	1	NM_030636.3	ENSP00000242108	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 16, 2023

The c.170C>T (p.T57M) alteration is located in exon 2 (coding exon 1) of the EEPD1 gene. This alteration results from a C to T substitution at nucleotide position 170, causing the threonine (T) at amino acid position 57 to be replaced by a methionine (M). 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	Uncertain	0.51
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.97	.;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.8	M;M
MutationTaster	Benign	0.95	D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		1.0	D;D
Vest4		0.62
MutPred		0.75		Gain of MoRF binding (P = 0.0742);Gain of MoRF binding (P = 0.0742);
MVP		0.67
MPC		1.3
ClinPred		0.99	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.55

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: chr7-36194103;