rs722722

Positions:

• chr5-94994096-T-C

Variant summary

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

The NM_024717.7(MCTP1):​c.838+23271A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,156 control chromosomes in the GnomAD database, including 1,750 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 0.12 (1750 hom., cov: 32)
• Consequence: MCTP1 NM_024717.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCTP1	NM_024717.7	c.838+23271A>G		intron_variant		ENST00000515393.6	NP_078993.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCTP1	ENST00000515393.6	c.838+23271A>G		intron_variant		1	NM_024717.7	ENSP00000424126.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18880 AN: 152038 Hom.: 1745 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.0705

Gnomad ASJ AF: 0.0495

Gnomad EAS AF: 0.0860

Gnomad SAS AF: 0.0482

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0616

Gnomad OTH AF: 0.0947

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

GnomAD4 genome AF: 0.124 AC: 18920 AN: 152156 Hom.: 1750 Cov.: 32 AF XY: 0.127 AC XY: 9435 AN XY: 74364

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.0704

Gnomad4 ASJ AF: 0.0495

Gnomad4 EAS AF: 0.0864

Gnomad4 SAS AF: 0.0477

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.0616

Gnomad4 OTH AF: 0.0966

Alfa AF: 0.0682 Hom.: 668

Bravo AF: 0.122

Asia WGS AF: 0.119 AC: 414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.69

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: rs722722; hg19: chr5-94329800;