NM_014016.5:c.551_552delGGinsTA

Variant names:

• chr3-45714053-GG-TA
• NM_014016.5:c.551_552delGGinsTA
• SACM1L p.Arg184Leu

Variant summary

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

The NM_014016.5(SACM1L):​c.551_552delGGinsTA​(p.Arg184Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. R184Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SACM1L NM_014016.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.79
• Publications: 0 publications found

Genes affected

SACM1L (HGNC:17059): (SAC1 like phosphatidylinositide phosphatase) This gene encodes an integral membrane protein, which is localized to the endoplasmic reticulum, and functions as a phosphoinositide phosphatase that hydrolyzes phosphatidylinositol 3-phosphate, phosphatidylinositol 4-phosphate, and phosphatidylinositol 3,5-bisphosphate. Deletion of this gene in mouse results in preimplantation lethality. Other studies suggest that this gene is also involved in the organization of golgi membranes and mitotic spindles. Alternatively spliced transcript variants have been found for this gene. A C-terminally extended isoform is also predicted to be produced by the use of an alternative in-frame, downstream translation termination codon via a stop codon readthrough mechanism.[provided by RefSeq, Dec 2017]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014016.5. 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
	SACM1L	NM_014016.5	MANE Select	c.551_552delGGinsTA	p.Arg184Leu	missense	N/A	NP_054735.3
	SACM1L	NM_001319071.2		c.551_552delGGinsTA	p.Arg184Leu	missense	N/A	NP_001306000.1	A0A5F9ZHN7
	SACM1L	NM_001319072.2		c.368_369delGGinsTA	p.Arg123Leu	missense	N/A	NP_001306001.1	Q9NTJ5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SACM1L	ENST00000389061.10	TSL:1 MANE Select	c.551_552delGGinsTA	p.Arg184Leu	missense	N/A	ENSP00000373713.4	Q9NTJ5-1
	SACM1L	ENST00000455997.5	TSL:1	n.242_243delGGinsTA		non_coding_transcript_exon	Exon 7 of 20	ENSP00000389975.1	F8WDN7
	SACM1L	ENST00000672858.2		c.551_552delGGinsTA	p.Arg184Leu	missense	N/A	ENSP00000500542.2	A0A5F9ZHN7

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.8

Splicing

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: chr3-45755545;