14-24139129-G-C

Position:

• chr14-24139129-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016049.4(EMC9):​c.508C>G​(p.Gln170Glu) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EMC9 NM_016049.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.27

Genes affected

EMC9 (HGNC:20273): (ER membrane protein complex subunit 9) Contributes to membrane insertase activity. Involved in protein insertion into ER membrane by stop-transfer membrane-anchor sequence and tail-anchored membrane protein insertion into ER membrane. Located in cytoplasm. Part of EMC complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059821695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMC9	NM_016049.4	c.508C>G	p.Gln170Glu	missense_variant	6/6	ENST00000216799.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMC9	ENST00000216799.9	c.508C>G	p.Gln170Glu	missense_variant	6/6	1	NM_016049.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Dec 20, 2023

The c.508C>G (p.Q170E) alteration is located in exon 6 (coding exon 5) of the EMC9 gene. This alteration results from a C to G substitution at nucleotide position 508, causing the glutamine (Q) at amino acid position 170 to be replaced by a glutamic acid (E). 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	0.075
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.73
DEOGEN2	Benign	0.0066	T;T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.63	D
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.060	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.98	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.33	N;N;N
Sift	Benign	0.81	T;T;T
Sift4G	Benign	0.96	T;T;T
Polyphen		0.0010	.;B;B
Vest4		0.10
MutPred		0.48		.;Gain of catalytic residue at D166 (P = 0.0061);Gain of catalytic residue at D166 (P = 0.0061);
MVP		0.36
MPC		0.24
ClinPred		0.034	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.070
gMVP		0.20

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: chr14-24608338;