NM_138704.4:c.814A>G

Variant names:

• chr15-29268892-T-C
• rs1340560807
• NM_138704.4:c.814A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138704.4(NSMCE3):​c.814A>G​(p.Asn272Asp) 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. 13/21 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: NSMCE3 NM_138704.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.81
• Publications: 0 publications found

Genes affected

NSMCE3 (HGNC:7677): (NSE3 homolog, SMC5-SMC6 complex component) The protein encoded by this gene is part of the SMC5-6 chromatin reorganizing complex and is a member of the MAGE superfamily. This is an intronless gene. [provided by RefSeq, May 2011]

ENTREP2 (HGNC:29075): (endosomal transmembrane epsin interactor 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06896451).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138704.4. 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
	NSMCE3	NM_138704.4	MANE Select	c.814A>G	p.Asn272Asp	missense	Exon 1 of 1	NP_619649.1	Q96MG7
	ENTREP2	NM_015307.2	MANE Select	c.277-16414A>G		intron	N/A	NP_056122.1	O60320-1
	ENTREP2	NM_001387214.1		c.277-16414A>G		intron	N/A	NP_001374143.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSMCE3	ENST00000332303.6	TSL:6 MANE Select	c.814A>G	p.Asn272Asp	missense	Exon 1 of 1	ENSP00000330694.4	Q96MG7
	ENTREP2	ENST00000261275.5	TSL:5 MANE Select	c.277-16414A>G		intron	N/A	ENSP00000261275.4	O60320-1
	ENTREP2	ENST00000918355.1		c.277-16414A>G		intron	N/A	ENSP00000588414.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.91	T
PhyloP100		1.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.028
Sift	Benign	0.18	T
Sift4G	Benign	0.88	T
Polyphen		0.0020	B
Vest4		0.36
MutPred		0.38		Loss of MoRF binding (P = 0.0442)
MVP		0.14
MPC		0.52
ClinPred		0.061	T
GERP RS		1.5
Varity_R		0.38
gMVP		0.14

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: rs1340560807; hg19: chr15-29561096;