TM4SF1 p.Cys107Ser

Variant names:

• chr3-149375536-C-G
• rs994955712
• NM_014220.3:c.320G>C
• TM4SF1 p.Cys107Ser

Your query was ambiguous. Multiple possible variants found:

• chr3-149375536-C-G
• chr3-149375537-A-T
• chr3-149375535-AC-GG
• chr3-149375535-AC-TG
• chr3-149375535-AC-CG
• chr3-149375535-ACA-GCT

Variant summary

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

The NM_014220.3(TM4SF1):​c.320G>C​(p.Cys107Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C107G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TM4SF1 NM_014220.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.07
• Publications: 3 publications found

Genes affected

TM4SF1 (HGNC:11853): (transmembrane 4 L six family member 1) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface antigen and is highly expressed in different carcinomas. [provided by RefSeq, Jul 2008]

TM4SF1-AS1 (HGNC:40587): (TM4SF1 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, 0.941

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014220.3. 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
	TM4SF1	NM_014220.3	MANE Select	c.320G>C	p.Cys107Ser	missense	Exon 3 of 5	NP_055035.1	P30408
	TM4SF1	NM_001410837.1		c.267+144G>C		intron	N/A	NP_001397766.1	F8WF27

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TM4SF1	ENST00000305366.8	TSL:1 MANE Select	c.320G>C	p.Cys107Ser	missense	Exon 3 of 5	ENSP00000304277.3	P30408
	TM4SF1	ENST00000868324.1		c.320G>C	p.Cys107Ser	missense	Exon 3 of 5	ENSP00000538383.1
	TM4SF1	ENST00000472441.1	TSL:2	c.53G>C	p.Cys18Ser	missense	Exon 1 of 2	ENSP00000417084.1	C9J611

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.94	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.8	L
PhyloP100		6.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.52
Sift	Benign	0.57	T
Sift4G	Benign	0.36	T
PromoterAI		-0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.69
Mutation Taster		=39/61	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs994955712;

hg19: chr3-149093323;