NM_032464.3:c.38C>T

Variant names:

• chr7-74216013-C-T
• rs543294747
• NM_032464.3:c.38C>T

Variant summary

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

The NM_032464.3(LAT2):​c.38C>T​(p.Ala13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: LAT2 NM_032464.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.549
• Publications: 0 publications found

Genes affected

LAT2 (HGNC:12749): (linker for activation of T cells family member 2) This gene is one of the contiguous genes at 7q11.23 commonly deleted in Williams syndrome, a multisystem developmental disorder. This gene consists of at least 14 exons, and its alternative splicing generates 3 transcript variants, all encoding the same protein. [provided by RefSeq, Jul 2008]

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=0.10116318).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032464.3. 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
	LAT2	NM_032464.3	MANE Select	c.38C>T	p.Ala13Val	missense	Exon 3 of 14	NP_115853.2	Q9GZY6-1
	LAT2	NM_014146.4		c.38C>T	p.Ala13Val	missense	Exon 2 of 13	NP_054865.2
	LAT2	NM_032463.3		c.38C>T	p.Ala13Val	missense	Exon 3 of 14	NP_115852.1	Q9GZY6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAT2	ENST00000460943.6	TSL:1 MANE Select	c.38C>T	p.Ala13Val	missense	Exon 3 of 14	ENSP00000420494.1	Q9GZY6-1
	LAT2	ENST00000275635.11	TSL:1	c.38C>T	p.Ala13Val	missense	Exon 3 of 14	ENSP00000275635.7	Q9GZY6-1
	LAT2	ENST00000344995.9	TSL:1	c.38C>T	p.Ala13Val	missense	Exon 2 of 13	ENSP00000344881.5	Q9GZY6-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000201 AC: 5 AN: 248848 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461606 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 727120

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111960

Other (OTH) AF: 0.0000166 AC: 1 AN: 60382

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.55
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.058
Sift	Benign	0.092	T
Sift4G	Uncertain	0.019	D
Polyphen		0.10	B
Vest4		0.25
MutPred		0.24		Loss of helix (P = 0.0123)
MVP		0.28
MPC		0.21
ClinPred		0.21	T
GERP RS		1.2
Varity_R		0.071
gMVP		0.37
Mutation Taster		=100/0	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: rs543294747; hg19: chr7-73630343;