NM_001394674.1:c.129G>A

Variant names:

• chr3-9986533-C-T
• rs373587570
• NM_001394674.1:c.129G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001394674.1(EMC3):​c.129G>A​(p.Lys43Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EMC3 NM_001394674.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.687
• Publications: 0 publications found

Genes affected

EMC3 (HGNC:23999): (ER membrane protein complex subunit 3) 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. Is integral component of endoplasmic reticulum membrane. Part of EMC complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP7: Synonymous conserved (PhyloP=0.687 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394674.1. 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
	EMC3	NM_001394674.1	MANE Select	c.129G>A	p.Lys43Lys	synonymous	Exon 1 of 8	NP_001381603.1	Q9P0I2-1
	EMC3	NM_018447.4		c.129G>A	p.Lys43Lys	synonymous	Exon 2 of 9	NP_060917.1	Q9P0I2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMC3	ENST00000245046.7	TSL:1 MANE Select	c.129G>A	p.Lys43Lys	synonymous	Exon 1 of 8	ENSP00000245046.2	Q9P0I2-1
	EMC3	ENST00000487465.5	TSL:1	n.306G>A		non_coding_transcript_exon	Exon 1 of 7
	EMC3	ENST00000693754.1		c.129G>A	p.Lys43Lys	synonymous	Exon 1 of 9	ENSP00000509443.1	A0A8I5KS41

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461856 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	13
DANN	Benign	0.97
PhyloP100		0.69
PromoterAI		-0.092	Neutral

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: rs373587570; hg19: chr3-10028217;