7-143876098-G-C

Variant names:

• chr7-143876098-G-C
• rs1812683560
• NM_014719.3:c.511C>G

Variant summary

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

The NM_014719.3(TCAF1):​c.511C>G​(p.Pro171Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,568 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TCAF1 NM_014719.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.10

Genes affected

TCAF1 (HGNC:22201): (TRPM8 channel associated factor 1) Enables transmembrane transporter binding activity. Involved in negative regulation of cell migration; positive regulation of anion channel activity; and positive regulation of protein targeting to membrane. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCAF1	NM_014719.3	c.511C>G	p.Pro171Ala	missense_variant	Exon 2 of 9	ENST00000479870.6	NP_055534.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCAF1	ENST00000479870.6	c.511C>G	p.Pro171Ala	missense_variant	Exon 2 of 9	1	NM_014719.3	ENSP00000419235.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461568 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727010

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.511C>G (p.P171A) alteration is located in exon 2 (coding exon 1) of the TCAF1 gene. This alteration results from a C to G substitution at nucleotide position 511, causing the proline (P) at amino acid position 171 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-0.77	T
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-5.1	D;D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		1.0	D;.
Vest4		0.55
MutPred		0.70		Gain of catalytic residue at P171 (P = 0.0058);Gain of catalytic residue at P171 (P = 0.0058);
MVP		0.12
MPC		0.33
ClinPred		1.0	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.62
gMVP		0.68

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: rs1812683560; hg19: chr7-143573191;