rs1731062609

Variant names:

• chr3-149330347-A-C
• rs1731062609
• NM_138786.4:c.250T>G

Your query was ambiguous. Multiple possible variants found:

• chr3-149330347-A-C
• chr3-149330347-A-G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_138786.4(TM4SF18):​c.250T>G​(p.Cys84Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TM4SF18 NM_138786.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.87
• Publications: 0 publications found

Genes affected

TM4SF18 (HGNC:25181): (transmembrane 4 L six family member 18) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TM4SF18-AS1 (HGNC:56678): (TM4SF18 antisense RNA 1)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.949

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138786.4. 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
	TM4SF18	NM_138786.4	MANE Select	c.250T>G	p.Cys84Gly	missense	Exon 3 of 6	NP_620141.1	Q96CE8
	TM4SF18	NM_001184723.2		c.250T>G	p.Cys84Gly	missense	Exon 2 of 5	NP_001171652.1	Q96CE8
	TM4SF18-AS1	NR_186251.1		n.405-3157A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TM4SF18	ENST00000296059.7	TSL:1 MANE Select	c.250T>G	p.Cys84Gly	missense	Exon 3 of 6	ENSP00000296059.2	Q96CE8
	TM4SF18	ENST00000470080.5	TSL:2	c.250T>G	p.Cys84Gly	missense	Exon 2 of 5	ENSP00000419278.1	Q96CE8
	TM4SF18	ENST00000855970.1		c.250T>G	p.Cys84Gly	missense	Exon 3 of 6	ENSP00000526029.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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	0.11
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0082	T
MetaRNN	Pathogenic	0.95	D
MetaSVM	Benign	-0.79	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		4.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-8.5	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.081	T
Polyphen		1.0	D
Vest4		0.87
MutPred		0.86		Gain of disorder (P = 0.003)
MVP		0.61
MPC		0.63
ClinPred		1.0	D
GERP RS		4.1
Varity_R		0.58
gMVP		0.74
Mutation Taster		=60/40	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: rs1731062609; hg19: chr3-149048134;