Genetic Variant GTF2A1L:p.Gln195Pro (chr2-48646648-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006872.5(GTF2A1L):c.584A>C(p.Gln195Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. Q195R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GTF2A1L
NM_006872.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.80

Publications

0 publications found

Variant links:

Genes affected

GTF2A1L (HGNC:30727): (general transcription factor IIA subunit 1 like) The assembly and stability of the RNA polymerase II transcription pre-initiation complex on a eukaryotic core promoter involve the effects of transcription factor IIA (TFIIA) on the interaction between TATA-binding protein (TBP) and DNA. This gene encodes a germ cell-specific counterpart of the large (alpha/beta) subunit of general transcription factor TFIIA that is able to stabilize the binding of TBP to DNA and may be uniquely important to testis biology. Alternative splicing for this locus has been observed and two variants, encoding distinct isoforms, have been identified. Co-transcription of this gene and the neighboring upstream gene generates a rare transcript (SALF), which encodes a fusion protein comprised of sequence sharing identity with each individual gene product. [provided by RefSeq, Mar 2014]

GTF2A1L links:

STON1-GTF2A1L (HGNC:30651): (STON1-GTF2A1L readthrough) STON1-GTF2A1L mRNAs are infrequent but naturally occurring read-through products of the neighboring STON1 and GTF2A1L genes. These transcripts encode fusion proteins composed of the vast majority of each of the individual elements, stonin 1 and general transcription factor IIA, 1-like. Alternative splicing results in multiple transcript variants. The significance of these read-through variants and the function of the resulting protein products have not yet been determined. [provided by RefSeq, Oct 2010]

STON1-GTF2A1L links:

ENSG00000279956 (HGNC:):

ENSG00000279956 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25955275).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2A1L	NM_006872.5 link	c.584A>C	p.Gln195Pro	missense_variant	Exon 6 of 9	ENST00000403751.8	NP_006863.2	Q9UNN4-1A0A140VKA3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GTF2A1L	ENST00000403751.8 link	c.584A>C	p.Gln195Pro	missense_variant	Exon 6 of 9	1	NM_006872.5	ENSP00000384597.3	Q9UNN4-1
STON1-GTF2A1L	ENST00000394751.5 link	c.2555A>C	p.Gln852Pro	missense_variant	Exon 5 of 8	2		ENSP00000378234.3	A0A0A6YYG5
ENSG00000279956	ENST00000602369.3 link	n.*408-34T>G		intron_variant	Intron 11 of 12	5		ENSP00000473498.1	R4GN57

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111998

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.094

.;.;.;.;.;.;.;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.66

.;T;T;T;T;T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.26

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.8

.;.;.;.;.;.;.;L

PhyloP100

1.8

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.1

N;N;N;N;N;N;N;N

REVEL

Benign

0.20

Sift

Uncertain

0.019

D;D;D;D;D;D;D;D

Sift4G

Benign

0.19

T;T;T;T;T;T;T;T

Polyphen

0.0020

B;.;B;.;.;.;B;B

Vest4

0.30

MutPred

0.75

Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);.;.;.;.;.;

MVP

0.12

MPC

0.010, 0.0067

ClinPred

0.21

GERP RS

-0.31

Varity_R

0.24

gMVP

0.37

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over