rs2076375230

Variant names:

• chr2-227363743-C-G
• rs2076375230
• NM_024795.4:c.671G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-227363743-C-G
• chr2-227363743-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024795.4(TM4SF20):​c.671G>C​(p.Arg224Pro) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TM4SF20 NM_024795.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.672

Genes affected

TM4SF20 (HGNC:26230): (transmembrane 4 L six family member 20) The protein encoded by this gene is a member of the four-transmembrane L6 superfamily. Members of this family function in various cellular processes including cell proliferation, motility, and adhesion via their interactions with integrins. In human brain tissue, this gene is expressed at high levels in the parietal lobe, occipital lobe, hippocampus, pons, white matter, corpus callosum, and cerebellum. Knockout of the homologous gene in mouse results in a neurobehavioral phenotype with suggested enhanced motor coordination. A deletion mutation in the human gene is associated with specific language impairment-5. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17248598).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TM4SF20	NM_024795.4	c.671G>C	p.Arg224Pro	missense_variant	Exon 4 of 4	ENST00000304568.4	NP_079071.2
TM4SF20	XM_011511876.3	c.470G>C	p.Arg157Pro	missense_variant	Exon 5 of 5		XP_011510178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TM4SF20	ENST00000304568.4	c.671G>C	p.Arg224Pro	missense_variant	Exon 4 of 4	1	NM_024795.4	ENSP00000303028.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.085	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.080
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.027	D
Polyphen		0.058	B
Vest4		0.32
MutPred		0.58		Loss of MoRF binding (P = 0.0029);
MVP		0.40
MPC		0.012
ClinPred		0.46	T
GERP RS		1.1
Varity_R		0.42
gMVP		0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs2076375230; hg19: chr2-228228459;