X-101277652-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001168474.2(TAF7L):​c.645G>T​(p.Leu215Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000566 in 1,200,940 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., 5 hem., cov: 21)
Exomes 𝑓: 0.000040 ( 0 hom. 14 hem. )

Consequence

TAF7L
NM_001168474.2 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.282
Variant links:
Genes affected
TAF7L (HGNC:11548): (TATA-box binding protein associated factor 7 like) This gene is similar to a mouse gene that encodes a TATA box binding protein-associated factor, and shows testis-specific expression. The encoded protein could be a spermatogenesis-specific component of the DNA-binding general transcription factor complex TFIID. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.046617597).
BS2
High Hemizygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TAF7LNM_001168474.2 linkc.645G>T p.Leu215Phe missense_variant Exon 9 of 13 ENST00000356784.2 NP_001161946.1 Q5H9L4-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TAF7LENST00000356784.2 linkc.645G>T p.Leu215Phe missense_variant Exon 9 of 13 1 NM_001168474.2 ENSP00000349235.1 Q5H9L4-2
TAF7LENST00000372907.7 linkc.903G>T p.Leu301Phe missense_variant Exon 9 of 13 1 ENSP00000361998.3 Q5H9L4-1
TAF7LENST00000324762.10 linkc.645G>T p.Leu215Phe missense_variant Exon 8 of 11 2 ENSP00000320283.6 Q5H9L4-3

Frequencies

GnomAD3 genomes
AF:
0.000221
AC:
24
AN:
108781
Hom.:
0
Cov.:
21
AF XY:
0.000161
AC XY:
5
AN XY:
31105
show subpopulations
Gnomad AFR
AF:
0.000803
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000463
AC:
8
AN:
172913
Hom.:
0
AF XY:
0.0000342
AC XY:
2
AN XY:
58543
show subpopulations
Gnomad AFR exome
AF:
0.000476
Gnomad AMR exome
AF:
0.0000402
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000633
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000403
AC:
44
AN:
1092159
Hom.:
0
Cov.:
29
AF XY:
0.0000390
AC XY:
14
AN XY:
358623
show subpopulations
Gnomad4 AFR exome
AF:
0.00123
Gnomad4 AMR exome
AF:
0.0000295
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000190
Gnomad4 FIN exome
AF:
0.0000247
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000152
GnomAD4 genome
AF:
0.000221
AC:
24
AN:
108781
Hom.:
0
Cov.:
21
AF XY:
0.000161
AC XY:
5
AN XY:
31105
show subpopulations
Gnomad4 AFR
AF:
0.000803
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000136
Hom.:
0
Bravo
AF:
0.000268
ESP6500AA
AF:
0.000782
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000494
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 26, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.903G>T (p.L301F) alteration is located in exon 9 (coding exon 9) of the TAF7L gene. This alteration results from a G to T substitution at nucleotide position 903, causing the leucine (L) at amino acid position 301 to be replaced by a phenylalanine (F). 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
Benign
0.088
BayesDel_addAF
Benign
-0.80
T
BayesDel_noAF
Benign
-1.0
CADD
Benign
5.0
DANN
Benign
0.96
DEOGEN2
Benign
0.043
T;.;.
FATHMM_MKL
Benign
0.061
N
LIST_S2
Benign
0.33
T;T;T
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.047
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;.;.
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.63
N;N;N
REVEL
Benign
0.048
Sift
Benign
0.082
T;T;T
Sift4G
Benign
0.075
T;T;T
Polyphen
0.0050
B;B;.
Vest4
0.10
MutPred
0.15
Loss of phosphorylation at S304 (P = 0.1706);.;.;
MVP
0.043
MPC
0.30
ClinPred
0.0084
T
GERP RS
-1.8
Varity_R
0.063
gMVP
0.023

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs376330895; hg19: chrX-100532640; API