5-94894721-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_024717.7(MCTP1):c.1767A>G(p.Thr589=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,613,934 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (34 hom.)
• Consequence: MCTP1 NM_024717.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.78

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-94894721-T-C is Benign according to our data. Variant chr5-94894721-T-C is described in ClinVar as [Benign]. Clinvar id is 771381.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.78 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00194 (2830/1461598) while in subpopulation AMR AF= 0.0247 (1104/44708). AF 95% confidence interval is 0.0235. There are 34 homozygotes in gnomad4_exome. There are 1327 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCTP1	NM_024717.7	c.1767A>G	p.Thr589=	synonymous_variant	11/23	ENST00000515393.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCTP1	ENST00000515393.6	c.1767A>G	p.Thr589=	synonymous_variant	11/23	1	NM_024717.7	P2

Frequencies

GnomAD3 genomes AF: 0.00231 AC: 351 AN: 152218 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00739

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00635

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0117

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00557 AC: 1397 AN: 250928 Hom.: 20 AF XY: 0.00459 AC XY: 623 AN XY: 135608

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.0270

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00212

Gnomad SAS exome AF: 0.00173

Gnomad FIN exome AF: 0.0111

Gnomad NFE exome AF: 0.000856

Gnomad OTH exome AF: 0.00441

GnomAD4 exome AF: 0.00194 AC: 2830 AN: 1461598 Hom.: 34 Cov.: 32 AF XY: 0.00183 AC XY: 1327 AN XY: 727072

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.0247

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.00988

Gnomad4 SAS exome AF: 0.00160

Gnomad4 FIN exome AF: 0.0106

Gnomad4 NFE exome AF: 0.000444

Gnomad4 OTH exome AF: 0.00195

GnomAD4 genome AF: 0.00233 AC: 355 AN: 152336 Hom.: 3 Cov.: 32 AF XY: 0.00285 AC XY: 212 AN XY: 74496

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.00765

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00637

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.0117

Gnomad4 NFE AF: 0.000720

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000777 Hom.: 1

Bravo AF: 0.00273

Asia WGS AF: 0.0100 AC: 36 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000534

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.61
Dann	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs140944775; hg19: chr5-94230426;