rs780099847

Variant names:

• chr16-28985444-C-G
• rs780099847
• NM_001014987.2:c.27C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-28985444-C-G
• chr16-28985444-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001014987.2(LAT):​c.27C>G​(p.Cys9Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. C9C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LAT NM_001014987.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.94
• Publications: 0 publications found

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]

LAT Gene-Disease associations (from GenCC):

• severe combined immunodeficiency due to LAT deficiency

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000261067 (HGNC:):

ACMG classification

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=0.08070785).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001014987.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAT	NM_001014987.2	MANE Select	c.27C>G	p.Cys9Trp	missense	Exon 1 of 12	NP_001014987.1	O43561-2
	LAT	NM_001014989.2		c.135C>G	p.Cys45Trp	missense	Exon 2 of 13	NP_001014989.2	O43561-3
	LAT	NM_014387.4		c.27C>G	p.Cys9Trp	missense	Exon 1 of 11	NP_055202.1	O43561-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAT	ENST00000395456.7	TSL:1 MANE Select	c.27C>G	p.Cys9Trp	missense	Exon 1 of 12	ENSP00000378841.3	O43561-2
	LAT	ENST00000395461.7	TSL:1	c.135C>G	p.Cys45Trp	missense	Exon 2 of 13	ENSP00000378845.3	O43561-3
	LAT	ENST00000566177.5	TSL:1	c.27C>G	p.Cys9Trp	missense	Exon 1 of 10	ENSP00000456761.1	O43561-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461484 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727066

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111930

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	4.6
DANN	Benign	0.91
DEOGEN2	Uncertain	0.67	D
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.9
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.062
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.19	T
Polyphen		0.73	P
Vest4		0.26
MutPred		0.36		Loss of sheet (P = 0.0315)
MVP		0.34
MPC		1.3
ClinPred		0.21	T
GERP RS		-8.0
PromoterAI		0.0018	Neutral
Varity_R		0.30
gMVP		0.34
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs780099847; hg19: chr16-28996765;