16-28985444-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001014987.2(LAT):​c.27C>T​(p.Cys9Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,613,636 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: LAT NM_001014987.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 16-28985444-C-T is Benign according to our data. Variant chr16-28985444-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2910748.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.94 with no splicing effect.

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>T	p.Cys9Cys	synonymous	Exon 1 of 12	NP_001014987.1	O43561-2
	LAT	NM_001014989.2		c.135C>T	p.Cys45Cys	synonymous	Exon 2 of 13	NP_001014989.2	O43561-3
	LAT	NM_014387.4		c.27C>T	p.Cys9Cys	synonymous	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>T	p.Cys9Cys	synonymous	Exon 1 of 12	ENSP00000378841.3	O43561-2
	LAT	ENST00000395461.7	TSL:1	c.135C>T	p.Cys45Cys	synonymous	Exon 2 of 13	ENSP00000378845.3	O43561-3
	LAT	ENST00000566177.5	TSL:1	c.27C>T	p.Cys9Cys	synonymous	Exon 1 of 10	ENSP00000456761.1	O43561-5

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

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

GnomAD2 exomes AF: 0.0000359 AC: 9 AN: 250952 AF XY: 0.0000369

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000246 AC: 36 AN: 1461482 Hom.: 0 Cov.: 33 AF XY: 0.0000248 AC XY: 18 AN XY: 727064

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.0000671 AC: 3 AN: 44712

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

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86256

European-Finnish (FIN) AF: 0.0000564 AC: 3 AN: 53192

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

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1111930

Other (OTH) AF: 0.0000166 AC: 1 AN: 60378

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152154 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74312

African (AFR) AF: 0.0000241 AC: 1 AN: 41440

American (AMR) AF: 0.000589 AC: 9 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000680

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.96
DANN	Benign	0.78
PhyloP100		-2.9
PromoterAI		-0.0010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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;