14-105529741-C-G

Variant names:

• chr14-105529741-C-G
• NM_025268.4:c.907C>G

Variant summary

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

The NM_025268.4(TMEM121):​c.907C>G​(p.Pro303Ala) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: TMEM121 NM_025268.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.195
• Publications: 0 publications found

Genes affected

TMEM121 (HGNC:20511): (transmembrane protein 121) Predicted to be integral component of 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 (MetaRNN=0.037968427).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025268.4. 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
	TMEM121	NM_025268.4	MANE Select	c.907C>G	p.Pro303Ala	missense	Exon 2 of 2	NP_079544.1	Q9BTD3
	TMEM121	NM_001331238.2		c.907C>G	p.Pro303Ala	missense	Exon 2 of 2	NP_001318167.1	Q9BTD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM121	ENST00000392519.7	TSL:1 MANE Select	c.907C>G	p.Pro303Ala	missense	Exon 2 of 2	ENSP00000376304.2	Q9BTD3
	TMEM121	ENST00000903730.1		c.907C>G	p.Pro303Ala	missense	Exon 2 of 2	ENSP00000573789.1
	TMEM121	ENST00000903731.1		c.907C>G	p.Pro303Ala	missense	Exon 2 of 2	ENSP00000573790.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

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	0.059
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	2.5
DANN	Benign	0.66
DEOGEN2	Benign	0.029	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.36	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.20
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.044
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.080
MutPred		0.16		Loss of glycosylation at P304 (P = 0.0732)
MVP		0.030
MPC		1.2
ClinPred		0.072	T
GERP RS		2.3
Varity_R		0.043
gMVP		0.40
Mutation Taster		=93/7	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

hg19: chr14-105996078;