Genetic Variant NM_001098814.2:c.62-1370C>A (chr16-4206004-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001098814.2(SRL):c.62-1370C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000244 in 151,826 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00024 ( 0 hom., cov: 31)

Consequence

SRL
NM_001098814.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.661

Variant links:

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]

SRL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRL	NM_001098814.2 link	c.62-1370C>A		intron_variant	Intron 1 of 5	ENST00000399609.7	NP_001092284.1	Q86TD4-2B3KPP4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SRL	ENST00000399609.7 link	c.62-1370C>A	intron_variant	Intron 1 of 5	1	NM_001098814.2	ENSP00000382518.3	Q86TD4-2
SRL	ENST00000572111.1 link	n.1439+723C>A	intron_variant	Intron 2 of 6	1		ENSP00000461179.1	I3L4D6
SRL	ENST00000537996.1 link	c.-65-1370C>A	intron_variant	Intron 1 of 5	2		ENSP00000440350.1	Q86TD4-3

Frequencies

GnomAD3 genomes

AF:

0.000244

AC:

AN:

151826

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00

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

GnomAD4 genome

AF:

0.000244

AC:

AN:

151826

Hom.:

Cov.:

AF XY:

0.000270

AC XY:

AN XY:

74136

show subpopulations

Gnomad4 AFR

AF:

0.000170

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00000508

Hom.:

4186

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.1

DANN

Benign

0.59

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over