6-41735303-G-T

Variant names:

• chr6-41735303-G-T
• rs6939861
• NM_001271944.2:c.-23+47C>A

Variant summary

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

The NM_001271944.2(TFEB):​c.-23+47C>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TFEB NM_001271944.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346
• Publications: 0 publications found

Genes affected

TFEB (HGNC:11753): (transcription factor EB) Enables DNA-binding transcription factor activity; enzyme binding activity; and transcription cis-regulatory region binding activity. Involved in several processes, including cellular response to amino acid starvation; lysosome localization; and positive regulation of autophagy. Located in cytosol; lysosomal membrane; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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 (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271944.2. 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
	TFEB	NM_001271944.2	MANE Select	c.-23+47C>A		intron	N/A	NP_001258873.1	P19484-1
	TFEB	NM_001167827.3		c.20+843C>A		intron	N/A	NP_001161299.2	B0QYS6
	TFEB	NM_001271943.2		c.-23+47C>A		intron	N/A	NP_001258872.1	P19484-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFEB	ENST00000373033.6	TSL:1 MANE Select	c.-23+47C>A		intron	N/A	ENSP00000362124.1	P19484-1
	TFEB	ENST00000358871.6	TSL:1	c.20+843C>A		intron	N/A	ENSP00000351742.2	B0QYS6
	TFEB	ENST00000861508.1		c.-129+47C>A		intron	N/A	ENSP00000531567.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.77
PhyloP100		-0.35
PromoterAI		-0.067	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6939861; hg19: chr6-41703041;