rs255339

Variant names:

• chr5-94801110-C-T
• rs255339
• NM_024717.7:c.2437-1978G>A

Variant summary

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

The NM_024717.7(MCTP1):​c.2437-1978G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 151,940 control chromosomes in the GnomAD database, including 4,563 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 0.22 (4563 hom., cov: 33)
• Consequence: MCTP1 NM_024717.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 2 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 = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCTP1	NM_024717.7	c.2437-1978G>A		intron_variant	Intron 17 of 22	ENST00000515393.6	NP_078993.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCTP1	ENST00000515393.6	c.2437-1978G>A		intron_variant	Intron 17 of 22	1	NM_024717.7	ENSP00000424126.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33500 AN: 151820 Hom.: 4563 Cov.: 33

Gnomad AFR AF: 0.0647

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.220 AC: 33495 AN: 151940 Hom.: 4563 Cov.: 33 AF XY: 0.217 AC XY: 16110 AN XY: 74260

African (AFR) AF: 0.0645 AC: 2674 AN: 41480

American (AMR) AF: 0.211 AC: 3227 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1300 AN: 3464

East Asian (EAS) AF: 0.219 AC: 1136 AN: 5178

South Asian (SAS) AF: 0.272 AC: 1315 AN: 4826

European-Finnish (FIN) AF: 0.239 AC: 2510 AN: 10514

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20296 AN: 67890

Other (OTH) AF: 0.270 AC: 570 AN: 2112

Alfa AF: 0.222 Hom.: 849

Bravo AF: 0.210

Asia WGS AF: 0.271 AC: 934 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.53
DANN	Benign	0.53
PhyloP100		-1.1
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: rs255339; hg19: chr5-94136815;