Variant 2-27663834-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000696012.1(SLC4A1AP):c.-81G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000278 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

SLC4A1AP
ENST00000696012.1 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.181

Variant links:

Genes affected

SUPT7L (HGNC:30632): (SPT7 like, STAGA complex subunit gamma) SUPT7L is a protein subunit of the human STAGA complex (SPT3; (MIM 602947)/TAF9 (MIM 600822)/GCN5 (MIM 602301) acetyltransferase complex), which is a chromatin-modifying multiprotein complex (Martinez et al., 2001 [PubMed 11564863]).[supplied by OMIM, Apr 2009]

SUPT7L links:

SLC4A1AP (HGNC:13813): (solute carrier family 4 member 1 adaptor protein) Predicted to enable mRNA binding activity. Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC4A1AP links:

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=0.031218171).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	UniProt
SUPT7L	ENST00000404798.6 linkuse as main transcript	c.-595C>T	5_prime_UTR_variant	1/5	2	O94864-4
SLC4A1AP	ENST00000696012.1 linkuse as main transcript	c.-81G>A	5_prime_UTR_variant	1/13
SLC4A1AP	ENST00000696011.1 linkuse as main transcript	c.-81G>A	5_prime_UTR_variant, NMD_transcript_variant	1/15

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000147

AC:

AN:

251408

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000291

AC:

426

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000298

AC XY:

217

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000562

Gnomad4 NFE exome

AF:

0.000365

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000145

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000287

Hom.:

Bravo

AF:

0.000212

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2023

The c.82G>A (p.G28R) alteration is located in exon 1 (coding exon 1) of the SLC4A1AP gene. This alteration results from a G to A substitution at nucleotide position 82, causing the glycine (G) at amino acid position 28 to be replaced by an arginine (R). 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

0.10

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.64

Cadd

Benign

7.7

Dann

Benign

0.82

DEOGEN2

Benign

0.0029

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0093

M_CAP

Benign

0.0019

MetaRNN

Benign

0.031

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

0.030

N;.

REVEL

Benign

0.0080

Sift

Benign

0.53

T;.

Sift4G

Uncertain

0.038

D;D

Polyphen

0.0

B;B

Vest4

0.032

MutPred

0.26

Gain of MoRF binding (P = 0.0334);Gain of MoRF binding (P = 0.0334);

MVP

0.21

MPC

0.31

ClinPred

0.019

GERP RS

1.3

Varity_R

0.022

gMVP

0.066

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over