rs2742435

Positions:

• chr3-45699371-G-A
• chr3-45699371-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014016.5(SACM1L):​c.33-4067G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 150,980 control chromosomes in the GnomAD database, including 14,788 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 0.41 (14788 hom., cov: 33)
• Consequence: SACM1L NM_014016.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SACM1L	NM_014016.5	c.33-4067G>A		intron_variant		ENST00000389061.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SACM1L	ENST00000389061.10	c.33-4067G>A		intron_variant		1	NM_014016.5	P1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62542 AN: 150862 Hom.: 14778 Cov.: 33

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.414 AC: 62580 AN: 150980 Hom.: 14788 Cov.: 33 AF XY: 0.412 AC XY: 30391 AN XY: 73838

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.449

Alfa AF: 0.446 Hom.: 2739

Bravo AF: 0.403

Asia WGS AF: 0.275 AC: 950 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.61
DANN	Benign	0.10

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

LitVar

Other links and lift over

dbSNP: rs2742435; hg19: chr3-45740863;