7-143724382-C-G

Variant names:

• chr7-143724382-C-G
• NM_001363538.2:c.2190C>G
• TCAF2 p.Pro730Pro

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001363538.2(TCAF2):​c.2190C>G​(p.Pro730Pro) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P730P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 20)
• Consequence: TCAF2 NM_001363538.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220
• Publications: 0 publications found

Genes affected

TCAF2 (HGNC:26878): (TRPM8 channel associated factor 2) Enables transmembrane transporter binding activity. Involved in negative regulation of anion channel activity; positive regulation of cell migration; and positive regulation of protein targeting to membrane. Located in cell junction and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000291149 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.063).
• BP7: Synonymous conserved (PhyloP=0.022 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363538.2. 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
	TCAF2	NM_001363538.2	MANE Select	c.2190C>G	p.Pro730Pro	synonymous	Exon 7 of 8	NP_001350467.1	A6NFQ2-1
	TCAF2	NM_001438662.2		c.2190C>G	p.Pro730Pro	synonymous	Exon 7 of 8	NP_001425591.2
	TCAF2	NM_001438663.2		c.2190C>G	p.Pro730Pro	synonymous	Exon 8 of 9	NP_001425592.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCAF2	ENST00000684770.1	MANE Select	c.2190C>G	p.Pro730Pro	synonymous	Exon 7 of 8	ENSP00000506869.1	A6NFQ2-1
	TCAF2	ENST00000357344.9	TSL:1	c.2190C>G	p.Pro730Pro	synonymous	Exon 6 of 6	ENSP00000349902.4	A6NFQ2-2
	TCAF2	ENST00000441159.7	TSL:5	c.2190C>G	p.Pro730Pro	synonymous	Exon 6 of 7	ENSP00000404265.2	A6NFQ2-1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.8
DANN	Benign	0.84
PhyloP100		0.022

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

hg19: chr7-143421475;