7-143876545-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014719.3(TCAF1):​c.64G>A​(p.Glu22Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000842 in 1,543,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign 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. E22Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

TCAF1
NM_014719.3 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.99
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.044889927).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TCAF1NM_014719.3 linkc.64G>A p.Glu22Lys missense_variant Exon 2 of 9 ENST00000479870.6 NP_055534.2 Q9Y4C2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TCAF1ENST00000479870.6 linkc.64G>A p.Glu22Lys missense_variant Exon 2 of 9 1 NM_014719.3 ENSP00000419235.1 Q9Y4C2-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152212
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000213
AC:
4
AN:
188112
Hom.:
0
AF XY:
0.0000101
AC XY:
1
AN XY:
98850
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000122
Gnomad SAS exome
AF:
0.0000617
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000229
GnomAD4 exome
AF:
0.00000863
AC:
12
AN:
1391246
Hom.:
0
Cov.:
32
AF XY:
0.00000875
AC XY:
6
AN XY:
685714
show subpopulations
Gnomad4 AFR exome
AF:
0.0000322
Gnomad4 AMR exome
AF:
0.0000302
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000102
Gnomad4 SAS exome
AF:
0.0000278
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000370
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152212
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000829
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0027
T;.;T;.;T;.
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.58
FATHMM_MKL
Benign
0.54
D
LIST_S2
Benign
0.33
T;T;.;T;T;T
M_CAP
Benign
0.0020
T
MetaRNN
Benign
0.045
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.43
T
PROVEAN
Benign
0.060
N;N;N;N;N;N
REVEL
Benign
0.15
Sift
Benign
0.95
T;T;T;T;T;T
Sift4G
Benign
0.49
T;T;T;T;.;T
Polyphen
0.0010
B;.;.;.;.;.
Vest4
0.37
MutPred
0.39
Gain of methylation at E22 (P = 0.0188);Gain of methylation at E22 (P = 0.0188);Gain of methylation at E22 (P = 0.0188);Gain of methylation at E22 (P = 0.0188);Gain of methylation at E22 (P = 0.0188);Gain of methylation at E22 (P = 0.0188);
MVP
0.030
MPC
0.055
ClinPred
0.075
T
GERP RS
4.0
Varity_R
0.091
gMVP
0.72

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs774689603; hg19: chr7-143573638; API