16-4207312-C-T

Variant names:

• chr16-4207312-C-T
• rs75825892
• ENST00000572111.1:n.854G>A

Variant summary

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

The ENST00000572111.1(SRL):​n.854G>A 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 0.0307 in 456,846 control chromosomes in the GnomAD database, including 374 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 0.025 (95 hom., cov: 33)
  • Exomes 𝑓: 0.033 (279 hom.)
• Consequence: SRL ENST00000572111.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.986
• Publications: 4 publications found

Genes affected

SRL (HGNC:11295): (sarcalumenin) Predicted to enable GTP binding activity. Predicted to be involved in endocytosis and endosomal transport. Predicted to act upstream of or within response to muscle activity involved in regulation of muscle adaptation and store-operated calcium entry. Predicted to be located in sarcoplasmic reticulum lumen and sarcoplasmic reticulum membrane. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.009).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0612 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000572111.1. 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
	SRL	NM_001098814.2	MANE Select	c.62-2678G>A		intron	N/A	NP_001092284.1
	SRL	NM_001435440.1		c.854G>A	p.Ser285Asn	missense	Exon 2 of 7	NP_001422369.1
	SRL	NM_001323668.1		c.-651G>A		5_prime_UTR	Exon 2 of 7	NP_001310597.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRL	ENST00000572111.1	TSL:1	n.854G>A		non_coding_transcript_exon	Exon 2 of 7	ENSP00000461179.1
	SRL	ENST00000399609.7	TSL:1 MANE Select	c.62-2678G>A		intron	N/A	ENSP00000382518.3
	SRL	ENST00000537996.1	TSL:2	c.-65-2678G>A		intron	N/A	ENSP00000440350.1

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3842 AN: 152204 Hom.: 92 Cov.: 33

Gnomad AFR AF: 0.00485

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.0642

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0302

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0295

Gnomad OTH AF: 0.0272

GnomAD2 exomes AF: 0.0388 AC: 5328 AN: 137192 AF XY: 0.0358

Gnomad AFR exome AF: 0.00434

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.0304

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0275

Gnomad NFE exome AF: 0.0285

Gnomad OTH exome AF: 0.0351

GnomAD4 exome AF: 0.0334 AC: 10170 AN: 304524 Hom.: 279 Cov.: 0 AF XY: 0.0321 AC XY: 5560 AN XY: 173392

African (AFR) AF: 0.00394 AC: 34 AN: 8628

American (AMR) AF: 0.102 AC: 2774 AN: 27284

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 324 AN: 10790

East Asian (EAS) AF: 0.00 AC: 0 AN: 9210

South Asian (SAS) AF: 0.0312 AC: 1866 AN: 59744

European-Finnish (FIN) AF: 0.0265 AC: 341 AN: 12858

Middle Eastern (MID) AF: 0.0237 AC: 66 AN: 2782

European-Non Finnish (NFE) AF: 0.0272 AC: 4318 AN: 158966

Other (OTH) AF: 0.0313 AC: 447 AN: 14262

GnomAD4 genome AF: 0.0253 AC: 3849 AN: 152322 Hom.: 95 Cov.: 33 AF XY: 0.0257 AC XY: 1916 AN XY: 74478

African (AFR) AF: 0.00484 AC: 201 AN: 41562

American (AMR) AF: 0.0645 AC: 988 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 104 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0304 AC: 147 AN: 4830

European-Finnish (FIN) AF: 0.0279 AC: 296 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0295 AC: 2009 AN: 68026

Other (OTH) AF: 0.0270 AC: 57 AN: 2114

Alfa AF: 0.0256 Hom.: 71

Bravo AF: 0.0288

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.2
DANN	Benign	0.93
PhyloP100		-0.99
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: rs75825892; hg19: chr16-4257313;