3-45691023-T-G

Variant names:

• chr3-45691023-T-G
• rs2742421
• NM_014016.5:c.32+1526T>G

Variant summary

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

The NM_014016.5(SACM1L):​c.32+1526T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 152,034 control chromosomes in the GnomAD database, including 18,242 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 0.48 (18242 hom., cov: 32)
• Consequence: SACM1L NM_014016.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106
• Publications: 5 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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SACM1L	NM_014016.5	MANE Select	c.32+1526T>G		intron	N/A	NP_054735.3
	SACM1L	NM_001319071.2		c.32+1526T>G		intron	N/A	NP_001306000.1
	SACM1L	NM_001319072.2		c.-24+1526T>G		intron	N/A	NP_001306001.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SACM1L	ENST00000389061.10	TSL:1 MANE Select	c.32+1526T>G		intron	N/A	ENSP00000373713.4
	SACM1L	ENST00000455997.5	TSL:1	n.-278+636T>G		intron	N/A	ENSP00000389975.1
	SACM1L	ENST00000672858.2		c.32+1526T>G		intron	N/A	ENSP00000500542.2

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73327 AN: 151918 Hom.: 18232 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.483 AC: 73368 AN: 152034 Hom.: 18242 Cov.: 32 AF XY: 0.478 AC XY: 35533 AN XY: 74306

African (AFR) AF: 0.427 AC: 17690 AN: 41450

American (AMR) AF: 0.479 AC: 7319 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2120 AN: 3470

East Asian (EAS) AF: 0.238 AC: 1230 AN: 5178

South Asian (SAS) AF: 0.356 AC: 1712 AN: 4810

European-Finnish (FIN) AF: 0.545 AC: 5756 AN: 10562

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35860 AN: 67970

Other (OTH) AF: 0.508 AC: 1073 AN: 2112

Alfa AF: 0.446 Hom.: 5879

Bravo AF: 0.481

Asia WGS AF: 0.334 AC: 1165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.7
DANN	Benign	0.70
PhyloP100		-0.11
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: rs2742421; hg19: chr3-45732515;