12-57083648-T-C

Variant names:

• chr12-57083648-T-C
• rs2035545
• ENST00000553654.1:n.113+4303A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000553654.1(NEMP1):​n.113+4303A>G variant causes a intron 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NEMP1 ENST00000553654.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• Publications: 4 publications found

Genes affected

NEMP1 (HGNC:29001): (nuclear envelope integral membrane protein 1) Involved in nuclear membrane organization. Predicted to be located in nuclear inner membrane. Predicted to be integral component of membrane. Predicted to be active in nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000304975 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEMP1	XM_011538056.3	c.271+4166A>G		intron_variant	Intron 1 of 8		XP_011536358.1
NEMP1	XM_024448900.1	c.151+2901A>G		intron_variant	Intron 2 of 9		XP_024304668.1
NEMP1	XM_047428587.1	c.151+2901A>G		intron_variant	Intron 1 of 8		XP_047284543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEMP1	ENST00000553654.1	n.113+4303A>G		intron_variant	Intron 1 of 2	5
ENSG00000304975	ENST00000807484.1	n.*82A>G		downstream_gene_variant
ENSG00000304975	ENST00000807485.1	n.*85A>G		downstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 29

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.54
PhyloP100		-0.068

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2035545; hg19: chr12-57477431;