22-17119793-C-T

Variant names:

• chr22-17119793-C-T
• rs371550781
• NM_031890.4:c.1335G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_031890.4(TMEM121B):​c.1335G>A​(p.Glu445Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,431,504 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TMEM121B NM_031890.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.943
• Publications: 0 publications found

Genes affected

TMEM121B (HGNC:1844): (transmembrane protein 121B)

LINC01664 (HGNC:52452): (long intergenic non-protein coding RNA 1664)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=0.943 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031890.4. 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
	TMEM121B	NM_031890.4	MANE Select	c.1335G>A	p.Glu445Glu	synonymous	Exon 1 of 1	NP_114096.1	Q9BXQ6-1
	TMEM121B	NM_001163079.2		c.270G>A	p.Glu90Glu	synonymous	Exon 2 of 2	NP_001156551.1	Q9BXQ6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM121B	ENST00000331437.4	TSL:6 MANE Select	c.1335G>A	p.Glu445Glu	synonymous	Exon 1 of 1	ENSP00000329318.3	Q9BXQ6-1
	TMEM121B	ENST00000399875.1	TSL:2	c.270G>A	p.Glu90Glu	synonymous	Exon 2 of 2	ENSP00000382764.1	Q9BXQ6-2
	LINC01664	ENST00000846293.1		n.275C>T		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1431504 Hom.: 0 Cov.: 36 AF XY: 0.00000141 AC XY: 1 AN XY: 711010

African (AFR) AF: 0.00 AC: 0 AN: 33294

American (AMR) AF: 0.00 AC: 0 AN: 42376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25760

East Asian (EAS) AF: 0.00 AC: 0 AN: 39054

South Asian (SAS) AF: 0.00 AC: 0 AN: 84026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1105212

Other (OTH) AF: 0.00 AC: 0 AN: 59642

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	11
DANN	Uncertain	0.98
PhyloP100		0.94

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: rs371550781; hg19: chr22-17600683;