3-45706849-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_014016.5(SACM1L):​c.275C>G​(p.Ala92Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SACM1L
NM_014016.5 missense

Scores

6
10
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.858

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SACM1LNM_014016.5 linkc.275C>G p.Ala92Gly missense_variant 4/20 ENST00000389061.10 NP_054735.3 Q9NTJ5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SACM1LENST00000389061.10 linkc.275C>G p.Ala92Gly missense_variant 4/201 NM_014016.5 ENSP00000373713.4 Q9NTJ5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 22, 2023The c.275C>G (p.A92G) alteration is located in exon 4 (coding exon 4) of the SACM1L gene. This alteration results from a C to G substitution at nucleotide position 275, causing the alanine (A) at amino acid position 92 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.34
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.30
T
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.033
D
MetaRNN
Pathogenic
0.86
D
MetaSVM
Uncertain
-0.25
T
MutationAssessor
Uncertain
2.9
M
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-2.8
D
REVEL
Uncertain
0.39
Sift
Uncertain
0.0070
D
Sift4G
Uncertain
0.011
D
Polyphen
0.99
D
Vest4
0.86
MutPred
0.64
Loss of catalytic residue at A92 (P = 0.0381);
MVP
0.36
MPC
0.99
ClinPred
0.99
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.52
gMVP
0.69

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-45748341; API