GeneBe

rs140990828

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014822.4(SEC24D):​c.2959-9_2959-6delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000466 in 1,287,544 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000047 ( 0 hom. )

Consequence

SEC24D
NM_014822.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.42
Variant links:
Genes affected
SEC24D (HGNC:10706): (SEC24 homolog D, COPII coat complex component) The protein encoded by this gene is a member of the SEC24 subfamily of the SEC23/SEC24 family, which is involved in vesicle trafficking. The encoded protein has similarity to yeast Sec24p component of COPII. COPII is the coat protein complex responsible for vesicle budding from the ER. This gene product is implicated in the shaping of the vesicle, and also in cargo selection and concentration. Mutations in this gene have been associated with Cole-Carpenter syndrome, a disorder affecting bone formation, resulting in craniofacial malformations and bones that break easily. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SEC24DNM_014822.4 linkc.2959-9_2959-6delTTTT splice_region_variant, intron_variant Intron 22 of 22 ENST00000280551.11 NP_055637.2 O94855-1A8K6V0
SEC24DNM_001318066.2 linkc.2962-9_2962-6delTTTT splice_region_variant, intron_variant Intron 22 of 22 NP_001304995.1 O94855-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SEC24DENST00000280551.11 linkc.2959-9_2959-6delTTTT splice_region_variant, intron_variant Intron 22 of 22 1 NM_014822.4 ENSP00000280551.6 O94855-1
SEC24DENST00000511481.5 linkc.1852-9_1852-6delTTTT splice_region_variant, intron_variant Intron 15 of 15 1 ENSP00000425491.1 E9PDM8
SEC24DENST00000502830.1 linkn.288-9_288-6delTTTT splice_region_variant, intron_variant Intron 1 of 1 2
SEC24DENST00000505134.5 linkn.3090-9_3090-6delTTTT splice_region_variant, intron_variant Intron 17 of 17 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000286
AC:
4
AN:
139688
Hom.:
0
AF XY:
0.0000263
AC XY:
2
AN XY:
75930
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000251
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000466
AC:
6
AN:
1287544
Hom.:
0
AF XY:
0.00000313
AC XY:
2
AN XY:
638828
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000120
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000201
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs140990828; hg19: chr4-119644815; API