rs534834201

Variant names:

• chr2-17716775-T-A
• rs534834201
• NM_001142286.2:c.1312A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-17716775-T-A
• chr2-17716775-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001142286.2(SMC6):​c.1312A>T​(p.Ile438Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMC6 NM_001142286.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.849

Genes affected

SMC6 (HGNC:20466): (structural maintenance of chromosomes 6) Enables ubiquitin protein ligase binding activity. Involved in several processes, including cellular senescence; positive regulation of chromosome segregation; and telomere maintenance via recombination. Located in chromosome and nuclear body. Part of Smc5-Smc6 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10668966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMC6	NM_001142286.2	c.1312A>T	p.Ile438Leu	missense_variant	Exon 14 of 28	ENST00000448223.7	NP_001135758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMC6	ENST00000448223.7	c.1312A>T	p.Ile438Leu	missense_variant	Exon 14 of 28	1	NM_001142286.2	ENSP00000404092.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.041	T;T;T;.;.
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.71	.;.;T;T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L;L;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N;N;N;N;.
REVEL	Benign	0.055
Sift	Benign	0.14	T;T;T;T;.
Sift4G	Benign	0.51	T;T;T;T;.
Polyphen		0.014	B;B;B;B;.
Vest4		0.31
MutPred		0.48		Gain of ubiquitination at K442 (P = 0.2763);Gain of ubiquitination at K442 (P = 0.2763);Gain of ubiquitination at K442 (P = 0.2763);.;Gain of ubiquitination at K442 (P = 0.2763);
MVP		0.29
MPC		0.29
ClinPred		0.39	T
GERP RS		3.4
Varity_R		0.093
gMVP		0.31

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: rs534834201; hg19: chr2-17898042;