1-241996305-A-G

Variant names:

• chr1-241996305-A-G
• rs1665083941
• NM_001004343.3:c.302T>C

Variant summary

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

The NM_001004343.3(MAP1LC3C):​c.302T>C​(p.Met101Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: MAP1LC3C NM_001004343.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.35

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP1LC3C	NM_001004343.3	c.302T>C	p.Met101Thr	missense_variant	Exon 4 of 4	ENST00000357246.4	NP_001004343.1
MAP1LC3C	XM_005273139.4	c.302T>C	p.Met101Thr	missense_variant	Exon 5 of 5		XP_005273196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP1LC3C	ENST00000357246.4	c.302T>C	p.Met101Thr	missense_variant	Exon 4 of 4	1	NM_001004343.3	ENSP00000349785.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.302T>C (p.M101T) alteration is located in exon 4 (coding exon 4) of the MAP1LC3C gene. This alteration results from a T to C substitution at nucleotide position 302, causing the methionine (M) at amino acid position 101 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	0.0094	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Pathogenic	3.6	H
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.022	D
Polyphen		0.90	P
Vest4		0.39
MutPred		0.80		Loss of helix (P = 0.0237);
MVP		0.69
MPC		1.3
ClinPred		0.99	D
GERP RS		1.9
Varity_R		0.60
gMVP		0.72

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: rs1665083941; hg19: chr1-242159607;