rs867743099

Variant names:

• chr1-241996249-C-A
• rs867743099
• NM_001004343.3:c.358G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-241996249-C-A
• chr1-241996249-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001004343.3(MAP1LC3C):​c.358G>T​(p.Ala120Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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. A120T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MAP1LC3C NM_001004343.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26
• Publications: 0 publications found

Genes affected

MAP1LC3C (HGNC:13353): (microtubule associated protein 1 light chain 3 gamma) Autophagy is a highly regulated bulk degradation process that plays an important role in cellular maintenance and development. MAP1LC3C is an ortholog of the yeast autophagosome protein Atg8 (He et al., 2003 [PubMed 12740394]).[supplied by OMIM, Nov 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28757215).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004343.3. 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
	MAP1LC3C	NM_001004343.3	MANE Select	c.358G>T	p.Ala120Ser	missense	Exon 4 of 4	NP_001004343.1	Q9BXW4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP1LC3C	ENST00000357246.4	TSL:1 MANE Select	c.358G>T	p.Ala120Ser	missense	Exon 4 of 4	ENSP00000349785.3	Q9BXW4
	MAP1LC3C	ENST00000943070.1		c.358G>T	p.Ala120Ser	missense	Exon 5 of 5	ENSP00000613129.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.98	L
PhyloP100		4.3
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.13
Sift	Benign	0.41	T
Sift4G	Benign	0.57	T
Polyphen		0.0030	B
Vest4		0.43
MutPred		0.63		Gain of disorder (P = 0.0363)
MVP		0.35
MPC		1.2
ClinPred		0.97	D
GERP RS		2.3
Varity_R		0.44
gMVP		0.46
Mutation Taster		=70/30	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: rs867743099; hg19: chr1-242159551;