rs11195001

Positions:

• chr10-110134895-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016824.5(ADD3):​c.*1277T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,208 control chromosomes in the GnomAD database, including 4,263 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 0.13 (4263 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADD3 NM_016824.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.26

Genes affected

ADD3 (HGNC:245): (adducin 3) Adducins are heteromeric proteins composed of different subunits referred to as adducin alpha, beta and gamma. The three subunits are encoded by distinct genes and belong to a family of membrane skeletal proteins involved in the assembly of spectrin-actin network in erythrocytes and at sites of cell-cell contact in epithelial tissues. While adducins alpha and gamma are ubiquitously expressed, the expression of adducin beta is restricted to brain and hematopoietic tissues. Adducin, originally purified from human erythrocytes, was found to be a heterodimer of adducins alpha and beta. Polymorphisms resulting in amino acid substitutions in these two subunits have been associated with the regulation of blood pressure in an animal model of hypertension. Heterodimers consisting of alpha and gamma subunits have also been described. Structurally, each subunit is comprised of two distinct domains. The amino-terminal region is protease resistant and globular in shape, while the carboxy-terminal region is protease sensitive. The latter contains multiple phosphorylation sites for protein kinase C, the binding site for calmodulin, and is required for association with spectrin and actin. Alternatively spliced adducin gamma transcripts encoding different isoforms have been described. The functions of the different isoforms are not known. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADD3	NM_016824.5	c.*1277T>C		3_prime_UTR_variant	15/15	ENST00000356080.9	NP_058432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADD3	ENST00000356080.9	c.*1277T>C		3_prime_UTR_variant	15/15	1	NM_016824.5	ENSP00000348381.4
ADD3	ENST00000277900.12	c.*1277T>C		3_prime_UTR_variant	14/14	1		ENSP00000277900.8

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20006 AN: 152090 Hom.: 4239 Cov.: 32

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0576

Gnomad ASJ AF: 0.00894

Gnomad EAS AF: 0.00518

Gnomad SAS AF: 0.0217

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00373

Gnomad OTH AF: 0.101

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 404 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 242

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.132 AC: 20077 AN: 152208 Hom.: 4263 Cov.: 32 AF XY: 0.128 AC XY: 9502 AN XY: 74446

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.0574

Gnomad4 ASJ AF: 0.00894

Gnomad4 EAS AF: 0.00520

Gnomad4 SAS AF: 0.0209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00373

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0798 Hom.: 474

Bravo AF: 0.151

Asia WGS AF: 0.0410 AC: 144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11195001; hg19: chr10-111894653;