NM_007359.5:c.*919A>G

Variant names:

• chr17-40171324-A-G
• rs73306851
• NM_007359.5:c.*919A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_007359.5(CASC3):​c.*919A>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 0.0016 in 986,030 control chromosomes in the GnomAD database, including 22 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 0.0070 (14 hom., cov: 31)
  • Exomes 𝑓: 0.00060 (8 hom.)
• Consequence: CASC3 NM_007359.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185
• Publications: 1 publications found

Genes affected

CASC3 (HGNC:17040): (CASC3 exon junction complex subunit) The product of this gene is a core component of the exon junction complex (EJC), a protein complex that is deposited on spliced mRNAs at exon-exon junctions and functions in nonsense-mediated mRNA decay (NMD). The encoded protein binds RNA and interacts with two other EJC core components. It is predominantly located in the cytoplasm, but shuttles into the nucleus where it localizes to nuclear speckles. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00703 (1071/152280) while in subpopulation AFR AF = 0.0245 (1017/41550). AF 95% confidence interval is 0.0232. There are 14 homozygotes in GnomAd4. There are 499 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1071 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007359.5. 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
	CASC3	NM_007359.5	MANE Select	c.*919A>G		3_prime_UTR	Exon 14 of 14	NP_031385.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC3	ENST00000264645.12	TSL:1 MANE Select	c.*919A>G		3_prime_UTR	Exon 14 of 14	ENSP00000264645.6	O15234
	CASC3	ENST00000971362.1		c.*914A>G		3_prime_UTR	Exon 14 of 14	ENSP00000641421.1
	CASC3	ENST00000971363.1		c.*919A>G		3_prime_UTR	Exon 14 of 14	ENSP00000641422.1

Frequencies

GnomAD3 genomes AF: 0.00703 AC: 1069 AN: 152162 Hom.: 14 Cov.: 31

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

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: 0.0000735

Gnomad OTH AF: 0.00717

GnomAD4 exome AF: 0.000603 AC: 503 AN: 833750 Hom.: 8 Cov.: 31 AF XY: 0.000564 AC XY: 217 AN XY: 385086

African (AFR) AF: 0.0274 AC: 432 AN: 15788

American (AMR) AF: 0.00 AC: 0 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5152

East Asian (EAS) AF: 0.00 AC: 0 AN: 3770

South Asian (SAS) AF: 0.0000608 AC: 1 AN: 16460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 710

Middle Eastern (MID) AF: 0.00123 AC: 2 AN: 1620

European-Non Finnish (NFE) AF: 0.0000302 AC: 23 AN: 761960

Other (OTH) AF: 0.00165 AC: 45 AN: 27306

GnomAD4 genome AF: 0.00703 AC: 1071 AN: 152280 Hom.: 14 Cov.: 31 AF XY: 0.00670 AC XY: 499 AN XY: 74452

African (AFR) AF: 0.0245 AC: 1017 AN: 41550

American (AMR) AF: 0.00209 AC: 32 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68028

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.00319 Hom.: 3

Bravo AF: 0.00831

Asia WGS AF: 0.00173 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	4.6
DANN	Benign	0.75
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs73306851; hg19: chr17-38327577;