Variant rs786204846 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_014822.4(SEC24D):c.2933A>C(p.Gln978Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,453,678 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SEC24D
NM_014822.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.87

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 4-118728586-T-G is Pathogenic according to our data. Variant chr4-118728586-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 189341.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC24D	NM_014822.4 linkuse as main transcript	c.2933A>C	p.Gln978Pro	missense_variant	22/23	ENST00000280551.11	NP_055637.2
SEC24D	NM_001318066.2 linkuse as main transcript	c.2936A>C	p.Gln979Pro	missense_variant	22/23		NP_001304995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC24D	ENST00000280551.11 linkuse as main transcript	c.2933A>C	p.Gln978Pro	missense_variant	22/23	1	NM_014822.4	ENSP00000280551	P1	O94855-1
SEC24D	ENST00000511481.5 linkuse as main transcript	c.1826A>C	p.Gln609Pro	missense_variant	15/16	1		ENSP00000425491
SEC24D	ENST00000502830.1 linkuse as main transcript	n.262A>C		non_coding_transcript_exon_variant	1/2	2
SEC24D	ENST00000505134.5 linkuse as main transcript	n.3064A>C		non_coding_transcript_exon_variant	17/18	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000809

AC:

AN:

247294

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133444

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.00

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:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1453678

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

723236

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.00

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:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Cole-Carpenter syndrome 2

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 05, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.043

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.8

M;.

MutationTaster

Benign

0.95

D;D;D;D

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.7

D;D

REVEL

Uncertain

0.52

Sift

Benign

0.043

D;T

Sift4G

Uncertain

0.023

D;T

Polyphen

0.91

P;.

Vest4

0.87

MutPred

0.48

Loss of glycosylation at P982 (P = 0.0251);.;

MVP

0.50

MPC

0.61

ClinPred

0.89

GERP RS

5.8

Varity_R

0.94

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

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