Variant 3-45714053-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014016.5(SACM1L):c.551G>A(p.Arg184Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000072 in 1,527,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

SACM1L
NM_014016.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79

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]

SACM1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19056883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SACM1L	NM_014016.5 link	c.551G>A	p.Arg184Gln	missense_variant	7/20	ENST00000389061.10	NP_054735.3	Q9NTJ5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SACM1L	ENST00000389061.10 link	c.551G>A	p.Arg184Gln	missense_variant	7/20	1	NM_014016.5	ENSP00000373713.4		Q9NTJ5-1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151364

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000422

AC:

AN:

237126

Hom.:

AF XY:

0.00

AC XY:

AN XY:

128618

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000589

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000582

AC:

AN:

1375534

Hom.:

Cov.:

AF XY:

0.00000438

AC XY:

AN XY:

685602

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000788

Gnomad4 SAS exome

AF:

0.0000399

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.53e-7

Gnomad4 OTH exome

AF:

0.0000175

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151482

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73992

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000870

AC:

AN:

3462

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 submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.551G>A (p.R184Q) alteration is located in exon 7 (coding exon 7) of the SACM1L gene. This alteration results from a G to A substitution at nucleotide position 551, causing the arginine (R) at amino acid position 184 to be replaced by a glutamine (Q). 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

Benign

0.096

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

.;T

Eigen

Benign

-0.020

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.0083

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;L

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.93

N;N

REVEL

Benign

0.074

Sift

Benign

0.30

T;T

Sift4G

Benign

0.32

T;T

Polyphen

0.16

.;B

Vest4

0.42

MutPred

0.61

.;Loss of sheet (P = 0.1907);

MVP

0.17

MPC

0.49

ClinPred

0.38

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over