chr4-118723579-C-T

Variant names:

• chr4-118723579-C-T
• NM_014822.4:c.3035G>A

Variant summary

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

The NM_014822.4(SEC24D):​c.3035G>A​(p.Gly1012Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEC24D NM_014822.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57

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]

ACMG classification

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
SEC24D	NM_014822.4	c.3035G>A	p.Gly1012Glu	missense_variant	Exon 23 of 23	ENST00000280551.11	NP_055637.2
SEC24D	NM_001318066.2	c.3038G>A	p.Gly1013Glu	missense_variant	Exon 23 of 23		NP_001304995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC24D	ENST00000280551.11	c.3035G>A	p.Gly1012Glu	missense_variant	Exon 23 of 23	1	NM_014822.4	ENSP00000280551.6
SEC24D	ENST00000511481.5	c.1928G>A	p.Gly643Glu	missense_variant	Exon 16 of 16	1		ENSP00000425491.1
SEC24D	ENST00000502830.1	n.364G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
SEC24D	ENST00000505134.5	n.3166G>A		non_coding_transcript_exon_variant	Exon 18 of 18	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.
Eigen	Uncertain	0.63
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Uncertain	0.094	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Uncertain	0.11	D
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.8	D;D
REVEL	Uncertain	0.52
Sift	Benign	0.046	D;T
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;.
Vest4		0.75
MutPred		0.42		Gain of solvent accessibility (P = 0.012);.;
MVP		0.85
MPC		0.80
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.73
gMVP		0.59

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-119644734;