4-118723660-GAAAA-GAAAAAAAAAAAAAA

Variant names:

• chr4-118723660-G-GAAAAAAAAAA
• rs140990828
• NM_014822.4:c.2959-15_2959-6dupTTTTTTTTTT

Variant summary

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

The NM_014822.4(SEC24D):​c.2959-15_2959-6dupTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-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 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.471

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.2959-15_2959-6dupTTTTTTTTTT		splice_region_variant, intron_variant	Intron 22 of 22	ENST00000280551.11	NP_055637.2
SEC24D	NM_001318066.2	c.2962-15_2962-6dupTTTTTTTTTT		splice_region_variant, intron_variant	Intron 22 of 22		NP_001304995.1

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs140990828; hg19: chr4-119644815;