rs255339

Positions:

• chr5-94801110-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCTP1	NM_024717.7	c.2437-1978G>A		intron_variant		ENST00000515393.6	NP_078993.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCTP1	ENST00000515393.6	c.2437-1978G>A		intron_variant		1	NM_024717.7	ENSP00000424126	P2

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

Gnomad4 AFR AF: 0.0645

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.270

Alfa AF: 0.245 Hom.: 766

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

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: rs255339; hg19: chr5-94136815;