rs11953346

Variant names:

• chr5-94805742-T-C
• rs11953346
• NM_024717.7:c.2437-6610A>G

Variant summary

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

The NM_024717.7(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 NM_024717.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024717.7. 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
	MCTP1	NM_024717.7	MANE Select	c.2437-6610A>G		intron	N/A	NP_078993.4
	MCTP1	NM_001393535.1		c.2359-6610A>G		intron	N/A	NP_001380464.1
	MCTP1	NM_001393536.1		c.2299-6610A>G		intron	N/A	NP_001380465.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCTP1	ENST00000515393.6	TSL:1 MANE Select	c.2437-6610A>G		intron	N/A	ENSP00000424126.1
	MCTP1	ENST00000312216.12	TSL:1	c.1774-6610A>G		intron	N/A	ENSP00000308957.8
	MCTP1	ENST00000429576.6	TSL:2	c.1636-26579A>G		intron	N/A	ENSP00000391639.2

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

African (AFR) AF: 0.131 AC: 5358 AN: 40864

American (AMR) AF: 0.237 AC: 3566 AN: 15040

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1136 AN: 3450

East Asian (EAS) AF: 0.0283 AC: 145 AN: 5126

South Asian (SAS) AF: 0.220 AC: 1029 AN: 4682

European-Finnish (FIN) AF: 0.338 AC: 3490 AN: 10312

Middle Eastern (MID) AF: 0.285 AC: 82 AN: 288

European-Non Finnish (NFE) AF: 0.376 AC: 25377 AN: 67548

Other (OTH) AF: 0.287 AC: 592 AN: 2060

Alfa AF: 0.348 Hom.: 13576

Bravo AF: 0.260

Asia WGS AF: 0.122 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.55
PhyloP100		-0.14
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: rs11953346; hg19: chr5-94141447; COSMIC: COSV56508578;