4-41954396-C-A

Variant names:

• chr4-41954396-C-A
• rs1507086
• ENST00000264452.9:n.*546C>A

Variant summary

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

The ENST00000264452.9(TMEM33):​n.*546C>A variant causes a non coding transcript exon 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: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM33 ENST00000264452.9 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.743
• Publications: 17 publications found

Genes affected

TMEM33 (HGNC:25541): (transmembrane protein 33) Involved in positive regulation of endoplasmic reticulum unfolded protein response; regulation of endoplasmic reticulum tubular network organization; and response to endoplasmic reticulum stress. Located in endoplasmic reticulum membrane; melanosome; and nuclear envelope. Is integral component of endoplasmic reticulum membrane. [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=-0.75).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM33	NM_018126.3	c.*197C>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000504986.6	NP_060596.2
TMEM33	XM_005248116.5	c.*197C>A		3_prime_UTR_variant	Exon 8 of 8		XP_005248173.1
TMEM33	XM_005248117.3	c.*197C>A		3_prime_UTR_variant	Exon 8 of 8		XP_005248174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM33	ENST00000264452.9	n.*546C>A		non_coding_transcript_exon_variant	Exon 6 of 6	1		ENSP00000264452.5
TMEM33	ENST00000504986.6	c.*197C>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_018126.3	ENSP00000422473.1
TMEM33	ENST00000264452.9	n.*546C>A		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000264452.5
TMEM33	ENST00000513702.5	c.*197C>A		downstream_gene_variant		5		ENSP00000427006.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 367782 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 191066

African (AFR) AF: 0.00 AC: 0 AN: 9848

American (AMR) AF: 0.00 AC: 0 AN: 12112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10088

East Asian (EAS) AF: 0.00 AC: 0 AN: 24302

South Asian (SAS) AF: 0.00 AC: 0 AN: 27840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1510

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 241752

Other (OTH) AF: 0.00 AC: 0 AN: 20006

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 46353

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.9
DANN	Benign	0.82
PhyloP100		0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1507086; hg19: chr4-41956413;