3-45689959-C-T

Variant names:

• chr3-45689959-C-T
• rs2742417
• ENST00000455997.5:n.-706C>T

Variant summary

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

The ENST00000455997.5(SACM1L):​n.-706C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 167,192 control chromosomes in the GnomAD database, including 19,752 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 (18015 hom., cov: 34)
  • Exomes 𝑓: 0.47 (1737 hom.)
• Consequence: SACM1L ENST00000455997.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 23 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=-0.88).
• 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.32+462C>T		intron_variant	Intron 1 of 19	ENST00000389061.10	NP_054735.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SACM1L	ENST00000389061.10	c.32+462C>T		intron_variant	Intron 1 of 19	1	NM_014016.5	ENSP00000373713.4

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72917 AN: 151994 Hom.: 18004 Cov.: 34

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.471 AC: 7109 AN: 15078 Hom.: 1737 Cov.: 0 AF XY: 0.469 AC XY: 3654 AN XY: 7784

African (AFR) AF: 0.421 AC: 127 AN: 302

American (AMR) AF: 0.443 AC: 655 AN: 1480

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 214 AN: 332

East Asian (EAS) AF: 0.224 AC: 161 AN: 718

South Asian (SAS) AF: 0.368 AC: 688 AN: 1870

European-Finnish (FIN) AF: 0.495 AC: 200 AN: 404

Middle Eastern (MID) AF: 0.528 AC: 19 AN: 36

European-Non Finnish (NFE) AF: 0.511 AC: 4667 AN: 9142

Other (OTH) AF: 0.476 AC: 378 AN: 794

GnomAD4 genome AF: 0.480 AC: 72960 AN: 152114 Hom.: 18015 Cov.: 34 AF XY: 0.475 AC XY: 35333 AN XY: 74388

African (AFR) AF: 0.420 AC: 17387 AN: 41422

American (AMR) AF: 0.474 AC: 7257 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2116 AN: 3472

East Asian (EAS) AF: 0.238 AC: 1232 AN: 5186

South Asian (SAS) AF: 0.358 AC: 1729 AN: 4830

European-Finnish (FIN) AF: 0.536 AC: 5684 AN: 10598

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.527 AC: 35863 AN: 68002

Other (OTH) AF: 0.504 AC: 1062 AN: 2108

Alfa AF: 0.510 Hom.: 58137

Bravo AF: 0.478

Asia WGS AF: 0.335 AC: 1167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.58
DANN	Benign	0.72
PhyloP100		-1.2
PromoterAI		0.023	Neutral
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: rs2742417; hg19: chr3-45731451;