16-4207312-C-T

Position:

• chr16-4207312-C-T

Variant summary

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

The NM_001098814.2(SRL):​c.62-2678G>A variant causes a intron 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 NM_001098814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.986

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRL	NM_001098814.2	c.62-2678G>A		intron_variant		ENST00000399609.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRL	ENST00000399609.7	c.62-2678G>A		intron_variant		1	NM_001098814.2	P1
SRL	ENST00000572111.1	c.854G>A	p.Ser285Asn	missense_variant, NMD_transcript_variant	2/7	1
SRL	ENST00000537996.1	c.-65-2678G>A		intron_variant		2

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

GnomAD3 exomes AF: 0.0388 AC: 5328 AN: 137192 Hom.: 181 AF XY: 0.0358 AC XY: 2668 AN XY: 74560

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 SAS exome AF: 0.0302

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

Gnomad4 AFR exome AF: 0.00394

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.0300

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0312

Gnomad4 FIN exome AF: 0.0265

Gnomad4 NFE exome AF: 0.0272

Gnomad4 OTH exome AF: 0.0313

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

Gnomad4 AFR AF: 0.00484

Gnomad4 AMR AF: 0.0645

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0304

Gnomad4 FIN AF: 0.0279

Gnomad4 NFE AF: 0.0295

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0264 Hom.: 33

Bravo AF: 0.0288

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.2
DANN	Benign	0.93

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: rs75825892; hg19: chr16-4257313;