4-41954396-C-T

Variant names:

• chr4-41954396-C-T
• rs1507086
• NM_018126.3:c.*197C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018126.3(TMEM33):​c.*197C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 518,646 control chromosomes in the GnomAD database, including 141,063 homozygotes. 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: 𝑓 0.60 (32645 hom., cov: 31)
  • Exomes 𝑓: 0.76 (108418 hom.)
• Consequence: TMEM33 NM_018126.3 3_prime_UTR
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018126.3. 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
	TMEM33	NM_018126.3	MANE Select	c.*197C>T		3_prime_UTR	Exon 7 of 7	NP_060596.2	P57088

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM33	ENST00000504986.6	TSL:1 MANE Select	c.*197C>T		3_prime_UTR	Exon 7 of 7	ENSP00000422473.1	P57088
	TMEM33	ENST00000264452.9	TSL:1	n.*546C>T		non_coding_transcript_exon	Exon 6 of 6	ENSP00000264452.5	J3KN43
	TMEM33	ENST00000264452.9	TSL:1	n.*546C>T		3_prime_UTR	Exon 6 of 6	ENSP00000264452.5	J3KN43

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90358 AN: 151560 Hom.: 32637 Cov.: 31

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.894

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.615

GnomAD4 exome AF: 0.758 AC: 278334 AN: 366966 Hom.: 108418 Cov.: 6 AF XY: 0.760 AC XY: 144903 AN XY: 190680

African (AFR) AF: 0.158 AC: 1551 AN: 9828

American (AMR) AF: 0.768 AC: 9286 AN: 12088

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 6851 AN: 10056

East Asian (EAS) AF: 0.967 AC: 23495 AN: 24296

South Asian (SAS) AF: 0.791 AC: 21996 AN: 27798

European-Finnish (FIN) AF: 0.808 AC: 16380 AN: 20282

Middle Eastern (MID) AF: 0.682 AC: 1026 AN: 1504

European-Non Finnish (NFE) AF: 0.761 AC: 183444 AN: 241154

Other (OTH) AF: 0.717 AC: 14305 AN: 19960

GnomAD4 genome AF: 0.596 AC: 90369 AN: 151680 Hom.: 32645 Cov.: 31 AF XY: 0.606 AC XY: 44962 AN XY: 74148

African (AFR) AF: 0.159 AC: 6558 AN: 41200

American (AMR) AF: 0.735 AC: 11208 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2314 AN: 3464

East Asian (EAS) AF: 0.957 AC: 4951 AN: 5174

South Asian (SAS) AF: 0.773 AC: 3717 AN: 4808

European-Finnish (FIN) AF: 0.811 AC: 8575 AN: 10568

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.747 AC: 50736 AN: 67912

Other (OTH) AF: 0.619 AC: 1304 AN: 2108

Alfa AF: 0.688 Hom.: 46353

Bravo AF: 0.572

Asia WGS AF: 0.810 AC: 2810 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.84
PhyloP100		0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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;