16-28985404-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001014989.2(LAT):​c.95G>A​(p.Arg32Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00245 in 1,613,142 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 42 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 38 hom. )

Consequence

LAT
NM_001014989.2 missense

Scores

1
1
13

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.24
Variant links:
Genes affected
LAT (HGNC:18874): (linker for activation of T cells) The protein encoded by this gene is phosphorylated by ZAP-70/Syk protein tyrosine kinases following activation of the T-cell antigen receptor (TCR) signal transduction pathway. This transmembrane protein localizes to lipid rafts and acts as a docking site for SH2 domain-containing proteins. Upon phosphorylation, this protein recruits multiple adaptor proteins and downstream signaling molecules into multimolecular signaling complexes located near the site of TCR engagement. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.002146989).
BP6
Variant 16-28985404-G-A is Benign according to our data. Variant chr16-28985404-G-A is described in ClinVar as [Benign]. Clinvar id is 777001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0129 (1958/152264) while in subpopulation AFR AF= 0.0444 (1846/41554). AF 95% confidence interval is 0.0427. There are 42 homozygotes in gnomad4. There are 934 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LATNM_001014987.2 linkc.-14G>A 5_prime_UTR_variant Exon 1 of 12 ENST00000395456.7 NP_001014987.1 O43561-2
LATNM_001014989.2 linkc.95G>A p.Arg32Gln missense_variant Exon 2 of 13 NP_001014989.2 O43561-3
LATNM_014387.4 linkc.-14G>A 5_prime_UTR_variant Exon 1 of 11 NP_055202.1 O43561-1A0A024QZD6
LATNM_001014988.2 linkc.-14G>A 5_prime_UTR_variant Exon 1 of 12 NP_001014988.1 O43561-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LATENST00000395456 linkc.-14G>A 5_prime_UTR_variant Exon 1 of 12 1 NM_001014987.2 ENSP00000378841.3 O43561-2

Frequencies

GnomAD3 genomes
AF:
0.0129
AC:
1956
AN:
152146
Hom.:
42
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0445
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00517
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000827
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000221
Gnomad OTH
AF:
0.00716
GnomAD3 exomes
AF:
0.00347
AC:
870
AN:
250448
Hom.:
24
AF XY:
0.00234
AC XY:
317
AN XY:
135432
show subpopulations
Gnomad AFR exome
AF:
0.0468
Gnomad AMR exome
AF:
0.00237
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000294
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000115
Gnomad OTH exome
AF:
0.00131
GnomAD4 exome
AF:
0.00136
AC:
1993
AN:
1460878
Hom.:
38
Cov.:
33
AF XY:
0.00117
AC XY:
849
AN XY:
726766
show subpopulations
Gnomad4 AFR exome
AF:
0.0473
Gnomad4 AMR exome
AF:
0.00259
Gnomad4 ASJ exome
AF:
0.0000766
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000220
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000675
Gnomad4 OTH exome
AF:
0.00322
GnomAD4 genome
AF:
0.0129
AC:
1958
AN:
152264
Hom.:
42
Cov.:
32
AF XY:
0.0125
AC XY:
934
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.0444
Gnomad4 AMR
AF:
0.00510
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000828
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000221
Gnomad4 OTH
AF:
0.00709
Alfa
AF:
0.00537
Hom.:
10
Bravo
AF:
0.0150
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.0471
AC:
207
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.00425
AC:
516
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000237

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.74
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
1.8
DANN
Uncertain
1.0
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.48
T
MetaRNN
Benign
0.0021
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.12
N
REVEL
Benign
0.015
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.54
T
Vest4
0.070
MVP
0.095
MPC
0.75
ClinPred
0.038
T
GERP RS
-0.085
gMVP
0.16

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: rs77760721; hg19: chr16-28996725; COSMIC: COSV57956648; COSMIC: COSV57956648; API