NM_032928.4:c.8A>G

Variant names:

• chr9-136791378-A-G
• rs1336255589
• NM_032928.4:c.8A>G

Variant summary

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

The NM_032928.4(TMEM141):​c.8A>G​(p.Asn3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000576 in 1,561,688 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 (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: TMEM141 NM_032928.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0690
• Publications: 0 publications found

Genes affected

TMEM141 (HGNC:28211): (transmembrane protein 141) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000272896 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032928.4. 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
	TMEM141	NM_032928.4	MANE Select	c.8A>G	p.Asn3Ser	missense	Exon 1 of 5	NP_116317.1	Q96I45

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM141	ENST00000290079.9	TSL:1 MANE Select	c.8A>G	p.Asn3Ser	missense	Exon 1 of 5	ENSP00000290079.8	Q96I45
	TMEM141	ENST00000885942.1		c.8A>G	p.Asn3Ser	missense	Exon 1 of 5	ENSP00000556001.1
	TMEM141	ENST00000929972.1		c.8A>G	p.Asn3Ser	missense	Exon 1 of 4	ENSP00000600031.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152214 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

GnomAD2 exomes AF: 0.00000605 AC: 1 AN: 165328 AF XY: 0.0000112

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000156

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000568 AC: 8 AN: 1409474 Hom.: 0 Cov.: 33 AF XY: 0.00000574 AC XY: 4 AN XY: 696648

African (AFR) AF: 0.00 AC: 0 AN: 32018

American (AMR) AF: 0.00 AC: 0 AN: 37520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25354

East Asian (EAS) AF: 0.00 AC: 0 AN: 36372

South Asian (SAS) AF: 0.00 AC: 0 AN: 80364

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 0.00000737 AC: 8 AN: 1085326

Other (OTH) AF: 0.00 AC: 0 AN: 58394

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74372

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000378

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	0.15
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-0.069
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.18
Sift	Benign	0.19	T
Sift4G	Uncertain	0.020	D
Polyphen		0.073	B
Vest4		0.43
MutPred		0.49		Gain of disorder (P = 0.0556)
MVP		0.014
MPC		0.26
ClinPred		0.078	T
GERP RS		-4.8
PromoterAI		0.22	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.086
gMVP		0.86
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.43		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.43		Position offset: -5

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

Other links and lift over

dbSNP: rs1336255589; hg19: chr9-139685830;