rs10923

Positions:

• chr3-160434908-A-G

Variant summary

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

The NM_001002800.3(SMC4):​c.*1099A>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 0.21 in 152,118 control chromosomes in the GnomAD database, including 3,684 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 0.21 (3684 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SMC4 NM_001002800.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.533

Genes affected

SMC4 (HGNC:14013): (structural maintenance of chromosomes 4) This gene belongs to the 'structural maintenance of chromosomes' (SMC) gene family. Members of this gene family play a role in two changes in chromosome structure during mitotic segregation of chromosomes- chromosome condensation and sister chromatid cohesion. The protein encoded by this gene is likely a subunit of the 13S condensin complex, which is involved in chromosome condensation. A pseudogene related to this gene is located on chromosome 2. [provided by RefSeq, Jun 2016]

TRIM59-IFT80 (HGNC:):

TRIM59 (HGNC:30834): (tripartite motif containing 59) Predicted to enable ubiquitin protein ligase activity. Acts upstream of or within negative regulation of I-kappaB kinase/NF-kappaB signaling. Predicted to be located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMC4	NM_001002800.3	c.*1099A>G		3_prime_UTR_variant	24/24	ENST00000357388.8	NP_001002800.1
TRIM59-IFT80	NR_148401.1	n.1147+3324T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMC4	ENST00000357388.8	c.*1099A>G		3_prime_UTR_variant	24/24	1	NM_001002800.3	ENSP00000349961	P1
SMC4	ENST00000344722.5	c.*1099A>G		3_prime_UTR_variant	23/23	1		ENSP00000341382	P1
TRIM59	ENST00000543469.1	c.*965T>C		3_prime_UTR_variant	3/3	5		ENSP00000444313
SMC4	ENST00000462668.5	n.4189A>G		non_coding_transcript_exon_variant	16/16	2

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31902 AN: 152000 Hom.: 3688 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.210 AC: 31916 AN: 152118 Hom.: 3684 Cov.: 32 AF XY: 0.207 AC XY: 15407 AN XY: 74366

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.194

Alfa AF: 0.239 Hom.: 4357

Bravo AF: 0.208

Asia WGS AF: 0.158 AC: 550 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.2
DANN	Benign	0.67

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: rs10923; hg19: chr3-160152696;