15-29268892-T-A

Variant names:

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

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>T​(p.Asn272Tyr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N272D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NSMCE3 NM_138704.4 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.25984895).

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>T	p.Asn272Tyr	missense	Exon 1 of 1	NP_619649.1	Q96MG7
	ENTREP2	NM_015307.2	MANE Select	c.277-16414A>T		intron	N/A	NP_056122.1	O60320-1
	ENTREP2	NM_001387214.1		c.277-16414A>T		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>T	p.Asn272Tyr	missense	Exon 1 of 1	ENSP00000330694.4	Q96MG7
	ENTREP2	ENST00000261275.5	TSL:5 MANE Select	c.277-16414A>T		intron	N/A	ENSP00000261275.4	O60320-1
	ENTREP2	ENST00000918355.1		c.277-16414A>T		intron	N/A	ENSP00000588414.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251494 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.93	T
PhyloP100		1.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.035
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.050	T
Polyphen		0.82	P
Vest4		0.54
MutPred		0.40		Gain of phosphorylation at N272 (P = 0.03)
MVP		0.47
MPC		0.92
ClinPred		0.91	D
GERP RS		1.5
Varity_R		0.43
gMVP		0.28

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;