NM_031298.4:c.56T>C

Variant names:

• chr17-3669202-T-C
• NM_031298.4:c.56T>C

Variant summary

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

The NM_031298.4(EMC6):​c.56T>C​(p.Val19Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V19L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EMC6 NM_031298.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.20
• Publications: 0 publications found

Genes affected

EMC6 (HGNC:28430): (ER membrane protein complex subunit 6) Contributes to membrane insertase activity. Involved in autophagosome assembly; protein insertion into ER membrane by stop-transfer membrane-anchor sequence; and tail-anchored membrane protein insertion into ER membrane. Is integral component of endoplasmic reticulum membrane and integral component of omegasome membrane. Part of EMC complex. [provided by Alliance of Genome Resources, Apr 2022]

P2RX5-TAX1BP3 (HGNC:49191): (P2RX5-TAX1BP3 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring P2RX5 (purinergic receptor P2X, ligand-gated ion channel, 5) and TAX1BP3 (Tax1 binding protein 3) genes on chromosome 17. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031298.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMC6	NM_031298.4	MANE Select	c.56T>C	p.Val19Ala	missense	Exon 2 of 2	NP_112588.1	Q9BV81
	EMC6	NM_001014764.3		c.56T>C	p.Val19Ala	missense	Exon 2 of 2	NP_001014764.1	Q9BV81
	P2RX5-TAX1BP3	NR_037928.1		n.4950A>G		non_coding_transcript_exon	Exon 12 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMC6	ENST00000248378.6	TSL:1 MANE Select	c.56T>C	p.Val19Ala	missense	Exon 2 of 2	ENSP00000248378.4	Q9BV81
	P2RX5-TAX1BP3	ENST00000550383.1	TSL:2	n.*3252A>G		non_coding_transcript_exon	Exon 12 of 15	ENSP00000455681.1
	P2RX5-TAX1BP3	ENST00000550383.1	TSL:2	n.*3252A>G		3_prime_UTR	Exon 12 of 15	ENSP00000455681.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0096	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.9	L
PhyloP100		7.2
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.52
Sift	Benign	0.073	T
Sift4G	Benign	0.088	T
Polyphen		0.0020	B
Vest4		0.77
MutPred		0.71		Gain of relative solvent accessibility (P = 0.0023)
MVP		0.39
MPC		1.3
ClinPred		0.93	D
GERP RS		5.3
PromoterAI		0.0047	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.95

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

hg19: chr17-3572496;