chr5-95049359-G-A

Variant names:

• chr5-95049359-G-A
• rs17339892
• NM_024717.7:c.721-31875C>T

Variant summary

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

The NM_024717.7(MCTP1):​c.721-31875C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,022 control chromosomes in the GnomAD database, including 4,044 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 0.21 (4044 hom., cov: 32)
• Consequence: MCTP1 NM_024717.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.791
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.287 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.721-31875C>T		intron	N/A	NP_078993.4
	MCTP1	NM_001393535.1		c.721-31875C>T		intron	N/A	NP_001380464.1
	MCTP1	NM_001393536.1		c.721-31875C>T		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.721-31875C>T		intron	N/A	ENSP00000424126.1
	MCTP1	ENST00000312216.12	TSL:1	c.58-31875C>T		intron	N/A	ENSP00000308957.8
	MCTP1	ENST00000505208.5	TSL:1	c.58-31875C>T		intron	N/A	ENSP00000426438.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31837 AN: 151902 Hom.: 4040 Cov.: 32

Gnomad AFR AF: 0.0677

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.209 AC: 31841 AN: 152022 Hom.: 4044 Cov.: 32 AF XY: 0.204 AC XY: 15175 AN XY: 74294

African (AFR) AF: 0.0675 AC: 2798 AN: 41474

American (AMR) AF: 0.294 AC: 4483 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1124 AN: 3472

East Asian (EAS) AF: 0.112 AC: 579 AN: 5168

South Asian (SAS) AF: 0.178 AC: 854 AN: 4808

European-Finnish (FIN) AF: 0.199 AC: 2105 AN: 10570

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19210 AN: 67966

Other (OTH) AF: 0.227 AC: 479 AN: 2110

Alfa AF: 0.253 Hom.: 3924

Bravo AF: 0.211

Asia WGS AF: 0.133 AC: 461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.59
PhyloP100		0.79
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: rs17339892; hg19: chr5-94385063;