rs11953346

Positions:

• chr5-94805742-T-C

Variant summary

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

The ENST00000515393.6(MCTP1):​c.2437-6610A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 150,270 control chromosomes in the GnomAD database, including 6,600 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 0.27 (6600 hom., cov: 27)
• Consequence: MCTP1 ENST00000515393.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136

Genes affected

MCTP1 (HGNC:26183): (multiple C2 and transmembrane domain containing 1) Enables calcium ion binding activity. Predicted to be involved in several processes, including modulation of chemical synaptic transmission; negative regulation of endocytosis; and negative regulation of response to oxidative stress. Is integral component of membrane. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCTP1	NM_024717.7	c.2437-6610A>G		intron_variant		ENST00000515393.6	NP_078993.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCTP1	ENST00000515393.6	c.2437-6610A>G		intron_variant		1	NM_024717.7	ENSP00000424126	P2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 40952 AN: 150152 Hom.: 6600 Cov.: 27

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.0282

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.272 AC: 40947 AN: 150270 Hom.: 6600 Cov.: 27 AF XY: 0.267 AC XY: 19582 AN XY: 73250

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.0283

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.287

Alfa AF: 0.351 Hom.: 11497

Bravo AF: 0.260

Asia WGS AF: 0.122 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.55

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: rs11953346; hg19: chr5-94141447; COSMIC: COSV56508578;