rs2742423

Positions:

• chr3-45691938-A-G
• chr3-45691938-A-T

Variant summary

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

The NM_014016.5(SACM1L):​c.32+2441A>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 152,052 control chromosomes in the GnomAD database, including 18,252 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 (18252 hom., cov: 32)
• Consequence: SACM1L NM_014016.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.649

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=-0.98).
• 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/exons	MANE	Protein	UniProt
SACM1L	NM_014016.5	c.32+2441A>G		intron_variant		ENST00000389061.10	NP_054735.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SACM1L	ENST00000389061.10	c.32+2441A>G		intron_variant		1	NM_014016.5	ENSP00000373713	P1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73354 AN: 151934 Hom.: 18241 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.357

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: 73397 AN: 152052 Hom.: 18252 Cov.: 32 AF XY: 0.478 AC XY: 35562 AN XY: 74342

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.508

Alfa AF: 0.486 Hom.: 3062

Bravo AF: 0.480

Asia WGS AF: 0.334 AC: 1165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.2
DANN	Benign	0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2742423; hg19: chr3-45733430;