rs2245705

Variant names:

• chr3-45708230-T-C
• rs2245705
• NM_014016.5:c.334-1268T>C

Variant summary

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

The NM_014016.5(SACM1L):​c.334-1268T>C 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 152,010 control chromosomes in the GnomAD database, including 18,284 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 (18284 hom., cov: 32)
• Consequence: SACM1L NM_014016.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125
• Publications: 7 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=-0.91).
• 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.334-1268T>C		intron	N/A	NP_054735.3
	SACM1L	NM_001319071.2		c.334-1268T>C		intron	N/A	NP_001306000.1
	SACM1L	NM_001319072.2		c.151-1268T>C		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.334-1268T>C		intron	N/A	ENSP00000373713.4
	SACM1L	ENST00000455997.5	TSL:1	n.25-1268T>C		intron	N/A	ENSP00000389975.1
	SACM1L	ENST00000706804.1		n.1752T>C		non_coding_transcript_exon	Exon 4 of 16

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73384 AN: 151892 Hom.: 18274 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.483 AC: 73426 AN: 152010 Hom.: 18284 Cov.: 32 AF XY: 0.478 AC XY: 35545 AN XY: 74290

African (AFR) AF: 0.428 AC: 17756 AN: 41478

American (AMR) AF: 0.480 AC: 7322 AN: 15260

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

East Asian (EAS) AF: 0.237 AC: 1227 AN: 5182

South Asian (SAS) AF: 0.358 AC: 1724 AN: 4822

European-Finnish (FIN) AF: 0.544 AC: 5746 AN: 10554

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.528 AC: 35846 AN: 67926

Other (OTH) AF: 0.509 AC: 1075 AN: 2114

Alfa AF: 0.498 Hom.: 31617

Bravo AF: 0.481

Asia WGS AF: 0.333 AC: 1156 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.45
PhyloP100		-0.13
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: rs2245705; hg19: chr3-45749722;