NM_001146262.4:c.442+22756A>C

Variant names:

• chr1-210044010-A-C
• rs1413698
• NM_001146262.4:c.442+22756A>C

Variant summary

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

The NM_001146262.4(SYT14):​c.442+22756A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,058 control chromosomes in the GnomAD database, including 6,447 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 0.16 (6447 hom., cov: 32)
• Consequence: SYT14 NM_001146262.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.638
• Publications: 1 publications found

Genes affected

SYT14 (HGNC:23143): (synaptotagmin 14) This gene is a member of the synaptotagmin gene family and encodes a protein similar to other family members that mediate membrane trafficking in synaptic transmission. The encoded protein is a calcium-independent synaptotagmin. Mutations in this gene are a cause of autosomal recessive spinocerebellar ataxia-11 (SCAR11), and a t(1;3) translocation of this gene has been associated with neurodevelopmental abnormalities. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 4. [provided by RefSeq, Dec 2011]

SYT14 Gene-Disease associations (from GenCC):

• autosomal recessive spinocerebellar ataxia 11

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT14	NM_001146262.4	c.442+22756A>C		intron_variant	Intron 4 of 8	ENST00000367019.6	NP_001139734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT14	ENST00000367019.6	c.442+22756A>C		intron_variant	Intron 4 of 8	1	NM_001146262.4	ENSP00000355986.1
SYT14	ENST00000534859.2	c.208+22756A>C		intron_variant	Intron 1 of 5	1		ENSP00000442891.2

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24772 AN: 151940 Hom.: 6435 Cov.: 32

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0661

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.00815

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.163 AC: 24821 AN: 152058 Hom.: 6447 Cov.: 32 AF XY: 0.158 AC XY: 11718 AN XY: 74320

African (AFR) AF: 0.552 AC: 22846 AN: 41404

American (AMR) AF: 0.0660 AC: 1007 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4820

European-Finnish (FIN) AF: 0.00235 AC: 25 AN: 10622

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.00813 AC: 553 AN: 67996

Other (OTH) AF: 0.128 AC: 270 AN: 2108

Alfa AF: 0.101 Hom.: 493

Bravo AF: 0.186

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.59
PhyloP100		-0.64
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: rs1413698; hg19: chr1-210217355;