NM_198597.3:c.*109C>T

Variant names:

• chr10-73771204-C-T
• rs11541237
• NM_198597.3:c.*109C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_198597.3(SEC24C):​c.*109C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,307,972 control chromosomes in the GnomAD database, including 13,379 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1488 hom., cov: 32)
  • Exomes 𝑓: 0.14 (11891 hom.)
• Consequence: SEC24C NM_198597.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.651
• Publications: 13 publications found

Genes affected

SEC24C (HGNC:10705): (SEC24 homolog C, 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. The product of this gene may play a role in shaping the vesicle, as well as in cargo selection and concentration. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

SEC24C Gene-Disease associations (from GenCC):

• 22q11.2 deletion syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000279689 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198597.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC24C	NM_198597.3	MANE Select	c.*109C>T		3_prime_UTR	Exon 23 of 23	NP_940999.1	P53992-1
	SEC24C	NM_004922.4		c.*109C>T		3_prime_UTR	Exon 24 of 24	NP_004913.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC24C	ENST00000345254.9	TSL:1 MANE Select	c.*109C>T		3_prime_UTR	Exon 23 of 23	ENSP00000321845.6	P53992-1
	SEC24C	ENST00000465076.5	TSL:1	n.*502C>T		non_coding_transcript_exon	Exon 22 of 22	ENSP00000437000.1	G5EA31
	SEC24C	ENST00000465076.5	TSL:1	n.*502C>T		3_prime_UTR	Exon 22 of 22	ENSP00000437000.1	G5EA31

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20784 AN: 151956 Hom.: 1470 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.140 AC: 161433 AN: 1155898 Hom.: 11891 Cov.: 15 AF XY: 0.142 AC XY: 82207 AN XY: 577752

African (AFR) AF: 0.140 AC: 3674 AN: 26188

American (AMR) AF: 0.0918 AC: 2758 AN: 30046

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 4421 AN: 19236

East Asian (EAS) AF: 0.123 AC: 4686 AN: 37984

South Asian (SAS) AF: 0.216 AC: 14333 AN: 66392

European-Finnish (FIN) AF: 0.141 AC: 6490 AN: 46042

Middle Eastern (MID) AF: 0.167 AC: 566 AN: 3382

European-Non Finnish (NFE) AF: 0.133 AC: 117088 AN: 877182

Other (OTH) AF: 0.150 AC: 7417 AN: 49446

GnomAD4 genome AF: 0.137 AC: 20838 AN: 152074 Hom.: 1488 Cov.: 32 AF XY: 0.136 AC XY: 10131 AN XY: 74338

African (AFR) AF: 0.140 AC: 5807 AN: 41478

American (AMR) AF: 0.106 AC: 1618 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 794 AN: 3468

East Asian (EAS) AF: 0.123 AC: 637 AN: 5176

South Asian (SAS) AF: 0.195 AC: 941 AN: 4824

European-Finnish (FIN) AF: 0.133 AC: 1403 AN: 10572

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9154 AN: 67966

Other (OTH) AF: 0.129 AC: 272 AN: 2112

Alfa AF: 0.131 Hom.: 1880

Bravo AF: 0.136

Asia WGS AF: 0.149 AC: 520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.75
PhyloP100		0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11541237; hg19: chr10-75530962;