rs469339

Positions:

• chr5-94812833-G-A
• chr5-94812833-G-C
• chr5-94812833-G-T

Variant summary

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

The NM_024717.7(MCTP1):​c.2437-13701C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.962 in 151,518 control chromosomes in the GnomAD database, including 70,318 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 0.96 (70318 hom., cov: 27)
• Consequence: MCTP1 NM_024717.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCTP1	NM_024717.7	c.2437-13701C>T		intron_variant		ENST00000515393.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCTP1	ENST00000515393.6	c.2437-13701C>T		intron_variant		1	NM_024717.7	P2

Frequencies

GnomAD3 genomes AF: 0.962 AC: 145685 AN: 151400 Hom.: 70255 Cov.: 27

Gnomad AFR AF: 0.993

Gnomad AMI AF: 0.941

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.979

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.934

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.967

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

GnomAD4 genome AF: 0.962 AC: 145809 AN: 151518 Hom.: 70318 Cov.: 27 AF XY: 0.958 AC XY: 70849 AN XY: 73970

Gnomad4 AFR AF: 0.993

Gnomad4 AMR AF: 0.965

Gnomad4 ASJ AF: 0.979

Gnomad4 EAS AF: 0.753

Gnomad4 SAS AF: 0.870

Gnomad4 FIN AF: 0.934

Gnomad4 NFE AF: 0.969

Gnomad4 OTH AF: 0.965

Alfa AF: 0.969 Hom.: 14491

Bravo AF: 0.969

Asia WGS AF: 0.815 AC: 2836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.0
DANN	Benign	0.49

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: rs469339; hg19: chr5-94148538;