NM_001002800.3:c.*1099A>G

Variant names:

• chr3-160434908-A-G
• rs10923
• NM_001002800.3:c.*1099A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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:56756): (TRIM59-IFT80 readthrough (NMD candidate)) This locus represents naturally occurring readthrough transcription between the neighboring TRIM59 (tripartite motif containing 59) and IFT80 (intraflagellar transport 80) genes on chromosome 3. The readthrough transcript is unlikely to produce a protein product. [provided by RefSeq, Jun 2017]

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SMC4	NM_001002800.3	c.*1099A>G		3_prime_UTR_variant	Exon 24 of 24	ENST00000357388.8	NP_001002800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMC4	ENST00000357388.8	c.*1099A>G		3_prime_UTR_variant	Exon 24 of 24	1	NM_001002800.3	ENSP00000349961.3
TRIM59-IFT80	ENST00000483754.1	n.952+3324T>C		intron_variant	Intron 3 of 18	2		ENSP00000456272.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.132 AC: 5495 AN: 41512

American (AMR) AF: 0.249 AC: 3804 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3470

East Asian (EAS) AF: 0.139 AC: 722 AN: 5178

South Asian (SAS) AF: 0.226 AC: 1087 AN: 4820

European-Finnish (FIN) AF: 0.206 AC: 2176 AN: 10554

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17413 AN: 67996

Other (OTH) AF: 0.194 AC: 409 AN: 2110

Alfa AF: 0.239 Hom.: 5237

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
PhyloP100		0.53
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: rs10923; hg19: chr3-160152696;