Variant 4-118723660-GAAAA-GAAAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_014822.4(SEC24D):c.2959-7_2959-6dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,430,198 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

SEC24D
NM_014822.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.471

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]

SEC24D links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 4-118723660-G-GAA is Benign according to our data. Variant chr4-118723660-G-GAA is described in ClinVar as [Benign]. Clinvar id is 3673490.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC24D	NM_014822.4 link	c.2959-7_2959-6dupTT		splice_region_variant, intron_variant	Intron 22 of 22	ENST00000280551.11	NP_055637.2	O94855-1A8K6V0
SEC24D	NM_001318066.2 link	c.2962-7_2962-6dupTT		splice_region_variant, intron_variant	Intron 22 of 22		NP_001304995.1	O94855-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SEC24D	ENST00000280551.11 link	c.2959-6_2959-5insTT	splice_region_variant, intron_variant	Intron 22 of 22	1	NM_014822.4	ENSP00000280551.6	O94855-1
SEC24D	ENST00000511481.5 link	c.1852-6_1852-5insTT	splice_region_variant, intron_variant	Intron 15 of 15	1		ENSP00000425491.1	E9PDM8
SEC24D	ENST00000502830.1 link	n.288-6_288-5insTT	splice_region_variant, intron_variant	Intron 1 of 1	2
SEC24D	ENST00000505134.5 link	n.3090-6_3090-5insTT	splice_region_variant, intron_variant	Intron 17 of 17	2

Frequencies

GnomAD3 genomes

AF:

0.00000692

AC:

AN:

144518

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000153

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000265

AC:

AN:

139688

Hom.:

AF XY:

0.000237

AC XY:

AN XY:

75930

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000314

Gnomad ASJ exome

AF:

0.00181

Gnomad EAS exome

AF:

0.000106

Gnomad SAS exome

AF:

0.000581

Gnomad FIN exome

AF:

0.0000752

Gnomad NFE exome

AF:

0.000188

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000158

AC:

203

AN:

1285680

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

115

AN XY:

637908

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000211

Gnomad4 ASJ exome

AF:

0.000675

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000284

Gnomad4 FIN exome

AF:

0.0000859

Gnomad4 NFE exome

AF:

0.000148

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.00000692

AC:

AN:

144518

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70238

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000153

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over