5-94999455-G-C

Variant names:

• chr5-94999455-G-C
• rs10515220
• NM_024717.7:c.838+17912C>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.838+17912C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 151,998 control chromosomes in the GnomAD database, including 2,201 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 0.16 (2201 hom., cov: 33)
• Consequence: MCTP1 NM_024717.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 1 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 (EAS) allele frequency at 95% confidence interval = 0.315 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.838+17912C>G		intron	N/A	NP_078993.4
	MCTP1	NM_001393535.1		c.838+17912C>G		intron	N/A	NP_001380464.1
	MCTP1	NM_001393536.1		c.838+17912C>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.838+17912C>G		intron	N/A	ENSP00000424126.1
	MCTP1	ENST00000312216.12	TSL:1	c.175+17912C>G		intron	N/A	ENSP00000308957.8
	MCTP1	ENST00000505208.5	TSL:1	c.175+17912C>G		intron	N/A	ENSP00000426438.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24450 AN: 151880 Hom.: 2201 Cov.: 33

Gnomad AFR AF: 0.0926

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.161 AC: 24458 AN: 151998 Hom.: 2201 Cov.: 33 AF XY: 0.161 AC XY: 11983 AN XY: 74272

African (AFR) AF: 0.0927 AC: 3848 AN: 41494

American (AMR) AF: 0.121 AC: 1847 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 400 AN: 3466

East Asian (EAS) AF: 0.328 AC: 1693 AN: 5158

South Asian (SAS) AF: 0.241 AC: 1157 AN: 4802

European-Finnish (FIN) AF: 0.200 AC: 2102 AN: 10536

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12878 AN: 67948

Other (OTH) AF: 0.162 AC: 342 AN: 2114

Alfa AF: 0.169 Hom.: 273

Bravo AF: 0.150

Asia WGS AF: 0.257 AC: 891 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.20
DANN	Benign	0.59
PhyloP100		-1.0
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: rs10515220; hg19: chr5-94335159;