4-118723343-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014822.4(SEC24D):c.*172A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00271 in 578,128 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0074 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (5 hom.)
• Consequence: SEC24D NM_014822.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.37

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 4-118723343-T-C is Benign according to our data. Variant chr4-118723343-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1181948.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00743 (1131/152312) while in subpopulation AFR AF= 0.0253 (1052/41562). AF 95% confidence interval is 0.024. There are 7 homozygotes in gnomad4. There are 541 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC24D	NM_014822.4	c.*172A>G		3_prime_UTR_variant	23/23	ENST00000280551.11
SEC24D	NM_001318066.2	c.*172A>G		3_prime_UTR_variant	23/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC24D	ENST00000280551.11	c.*172A>G		3_prime_UTR_variant	23/23	1	NM_014822.4	P1
SEC24D	ENST00000511481.5	c.*172A>G		3_prime_UTR_variant	16/16	1
SEC24D	ENST00000505134.5	n.3402A>G		non_coding_transcript_exon_variant	18/18	2

Frequencies

GnomAD3 genomes AF: 0.00741 AC: 1127 AN: 152194 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00526

GnomAD4 exome AF: 0.00102 AC: 434 AN: 425816 Hom.: 5 Cov.: 6 AF XY: 0.000932 AC XY: 207 AN XY: 222198

Gnomad4 AFR exome AF: 0.0264

Gnomad4 AMR exome AF: 0.00238

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000906

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000126

Gnomad4 OTH exome AF: 0.00184

GnomAD4 genome AF: 0.00743 AC: 1131 AN: 152312 Hom.: 7 Cov.: 32 AF XY: 0.00726 AC XY: 541 AN XY: 74472

Gnomad4 AFR AF: 0.0253

Gnomad4 AMR AF: 0.00372

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00358 Hom.: 0

Bravo AF: 0.00892

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 18, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.065
Dann	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs79586191; hg19: chr4-119644498;