1-150579449-C-A

Variant names:

• chr1-150579449-C-A
• rs768684341
• NM_021960.5:c.82G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021960.5(MCL1):​c.82G>T​(p.Ala28Ser) 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. 14/22 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. A28T) 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: 0.634
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13000041).

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.82G>T	p.Ala28Ser	missense	Exon 1 of 3	NP_068779.1	Q07820-1
	MCL1	NM_182763.3		c.82G>T	p.Ala28Ser	missense	Exon 1 of 2	NP_877495.1	Q07820-2
	MCL1	NM_001197320.2		c.82G>T	p.Ala28Ser	missense	Exon 1 of 4	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.82G>T	p.Ala28Ser	missense	Exon 1 of 3	ENSP00000358022.2	Q07820-1
	MCL1	ENST00000307940.3	TSL:1	c.82G>T	p.Ala28Ser	missense	Exon 1 of 2	ENSP00000309973.3	Q07820-2
	MCL1	ENST00000620947.4	TSL:1	c.82G>T	p.Ala28Ser	missense	Exon 1 of 4	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	0.069
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.14	N
PhyloP100		0.63
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.037
Sift	Benign	0.17	T
Sift4G	Benign	0.16	T
Polyphen		0.29	B
Vest4		0.16
MutPred		0.16		Gain of glycosylation at A28 (P = 0.0071)
MVP		0.45
MPC		1.4
ClinPred		0.37	T
GERP RS		1.3
PromoterAI		-0.0090	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.084
gMVP		0.19
Mutation Taster		=96/4	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: rs768684341; hg19: chr1-150551925;