SNIP1 p.Glu387Asp

Variant names:

• chr1-37537778-C-A
• NM_024700.4:c.1161G>T
• SNIP1 p.Glu387Asp

Your query was ambiguous. Multiple possible variants found:

• chr1-37537778-C-A
• chr1-37537778-C-G

Variant summary

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

The NM_024700.4(SNIP1):​c.1161G>T​(p.Glu387Asp) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNIP1 NM_024700.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.86
• Publications: 0 publications found

Genes affected

SNIP1 (HGNC:30587): (Smad nuclear interacting protein 1) This gene encodes a protein that contains a coiled-coil motif and C-terminal forkhead-associated (FHA) domain. The encoded protein functions as a transcriptional coactivator that increases c-Myc activity and inhibits transforming growth factor beta (TGF-beta) and nuclear factor kappa-B (NF-kB) signaling. The encoded protein also regulates the stability of cyclin D1 mRNA, and may play a role in cell proliferation and cancer progression. Mutations in this gene are a cause of psychomotor retardation, epilepsy, and craniofacial dysmorphism (PMRED). [provided by RefSeq, Mar 2012]

SNIP1 Gene-Disease associations (from GenCC):

• psychomotor retardation, epilepsy, and craniofacial dysmorphism

  Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: Illumina, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P

ENSG00000307694 (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 (MetaRNN=0.01324895).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024700.4. 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
	SNIP1	NM_024700.4	MANE Select	c.1161G>T	p.Glu387Asp	missense	Exon 4 of 4	NP_078976.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNIP1	ENST00000296215.8	TSL:1 MANE Select	c.1161G>T	p.Glu387Asp	missense	Exon 4 of 4	ENSP00000296215.5	Q8TAD8
	SNIP1	ENST00000638725.1	TSL:2	n.1673G>T		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000307694	ENST00000827919.1		n.534-2357C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

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	Benign	0.068
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.0020
DANN	Benign	0.33
DEOGEN2	Benign	0.039	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		-2.9
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.51	N
REVEL	Benign	0.058
Sift	Benign	1.0	T
Sift4G	Benign	0.51	T
Varity_R		0.082
gMVP		0.18
Mutation Taster		=87/13	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-38003379;