22-17119963-G-A

Variant names:

• chr22-17119963-G-A
• rs1159344065
• NM_031890.4:c.1165C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031890.4(TMEM121B):​c.1165C>T​(p.Arg389Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000696 in 1,581,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R389L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: TMEM121B NM_031890.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.66
• Publications: 1 publications found

Genes affected

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

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17739591).

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.1165C>T	p.Arg389Trp	missense	Exon 1 of 1	NP_114096.1	Q9BXQ6-1
	TMEM121B	NM_001163079.2		c.100C>T	p.Arg34Trp	missense	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.1165C>T	p.Arg389Trp	missense	Exon 1 of 1	ENSP00000329318.3	Q9BXQ6-1
	TMEM121B	ENST00000399875.1	TSL:2	c.100C>T	p.Arg34Trp	missense	Exon 2 of 2	ENSP00000382764.1	Q9BXQ6-2
	LINC01664	ENST00000846293.1		n.445G>A		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152166 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000700 AC: 10 AN: 1428988 Hom.: 0 Cov.: 36 AF XY: 0.00000987 AC XY: 7 AN XY: 709504

African (AFR) AF: 0.00 AC: 0 AN: 33038

American (AMR) AF: 0.00 AC: 0 AN: 41174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25624

East Asian (EAS) AF: 0.00 AC: 0 AN: 38666

South Asian (SAS) AF: 0.00 AC: 0 AN: 84280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40290

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5712

European-Non Finnish (NFE) AF: 0.00000818 AC: 9 AN: 1100808

Other (OTH) AF: 0.00 AC: 0 AN: 59396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152166 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.094	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.7
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.10
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.023	D
Polyphen		0.0030	B
Vest4		0.23
MutPred		0.38		Loss of disorder (P = 0.0135)
MVP		0.39
ClinPred		0.33	T
GERP RS		1.9
Varity_R		0.14
gMVP		0.72
Mutation Taster		=74/26	polymorphism

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: rs1159344065; hg19: chr22-17600853; COSMIC: COSV58897176; COSMIC: COSV58897176;