rs1570983533

Variant names:

• chr1-150579227-T-A
• rs1570983533
• NM_021960.5:c.304A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-150579227-T-A
• chr1-150579227-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021960.5(MCL1):​c.304A>T​(p.Thr102Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T102P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MCL1 NM_021960.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669
• Publications: 0 publications found

Genes affected

MCL1 (HGNC:6943): (MCL1 apoptosis regulator, BCL2 family member) This gene encodes an anti-apoptotic protein, which is a member of the Bcl-2 family. Alternative splicing results in multiple transcript variants. The longest gene product (isoform 1) enhances cell survival by inhibiting apoptosis while the alternatively spliced shorter gene products (isoform 2 and isoform 3) promote apoptosis and are death-inducing. [provided by RefSeq, Oct 2010]

ENSG00000290074 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056777835).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021960.5. 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
	MCL1	NM_021960.5	MANE Select	c.304A>T	p.Thr102Ser	missense	Exon 1 of 3	NP_068779.1	Q07820-1
	MCL1	NM_182763.3		c.304A>T	p.Thr102Ser	missense	Exon 1 of 2	NP_877495.1	Q07820-2
	MCL1	NM_001197320.2		c.108+196A>T		intron	N/A	NP_001184249.1	A0A087WT64

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCL1	ENST00000369026.3	TSL:1 MANE Select	c.304A>T	p.Thr102Ser	missense	Exon 1 of 3	ENSP00000358022.2	Q07820-1
	MCL1	ENST00000307940.3	TSL:1	c.304A>T	p.Thr102Ser	missense	Exon 1 of 2	ENSP00000309973.3	Q07820-2
	MCL1	ENST00000620947.4	TSL:1	c.108+196A>T		intron	N/A	ENSP00000477624.1	A0A087WT64

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.1
DANN	Benign	0.59
DEOGEN2	Benign	0.22	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.67
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.041
Sift	Benign	0.43	T
Sift4G	Benign	0.49	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.064		Loss of glycosylation at T102 (P = 0.0994)
MVP		0.41
MPC		0.50
ClinPred		0.047	T
GERP RS		-0.33
PromoterAI		0.20	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.036
gMVP		0.18
Mutation Taster		=98/2	polymorphism

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: rs1570983533; hg19: chr1-150551703;