rs2742390

Variant names:

• chr3-45715230-G-A
• rs2742390
• NM_014016.5:c.577+1151G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014016.5(SACM1L):​c.577+1151G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,936 control chromosomes in the GnomAD database, including 18,437 homozygotes. 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: 𝑓 0.49 (18437 hom., cov: 32)
• Consequence: SACM1L NM_014016.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SACM1L	NM_014016.5	c.577+1151G>A		intron_variant	Intron 7 of 19	ENST00000389061.10	NP_054735.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SACM1L	ENST00000389061.10	c.577+1151G>A		intron_variant	Intron 7 of 19	1	NM_014016.5	ENSP00000373713.4

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73736 AN: 151818 Hom.: 18427 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.486 AC: 73779 AN: 151936 Hom.: 18437 Cov.: 32 AF XY: 0.481 AC XY: 35726 AN XY: 74232

African (AFR) AF: 0.436 AC: 18045 AN: 41428

American (AMR) AF: 0.481 AC: 7351 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2121 AN: 3472

East Asian (EAS) AF: 0.238 AC: 1229 AN: 5164

South Asian (SAS) AF: 0.357 AC: 1718 AN: 4806

European-Finnish (FIN) AF: 0.546 AC: 5746 AN: 10518

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.528 AC: 35880 AN: 67958

Other (OTH) AF: 0.511 AC: 1078 AN: 2108

Alfa AF: 0.499 Hom.: 32196

Bravo AF: 0.483

Asia WGS AF: 0.335 AC: 1168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.021
DANN	Benign	0.53
PhyloP100		-0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2742390; hg19: chr3-45756722;