chr7-74224036-T-G

Variant names:

• chr7-74224036-T-G
• rs371014575
• NM_032464.3:c.467T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032464.3(LAT2):​c.467T>G​(p.Ile156Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I156T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: LAT2 NM_032464.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513

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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04452434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAT2	NM_032464.3	c.467T>G	p.Ile156Arg	missense_variant	Exon 12 of 14	ENST00000460943.6	NP_115853.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAT2	ENST00000460943.6	c.467T>G	p.Ile156Arg	missense_variant	Exon 12 of 14	1	NM_032464.3	ENSP00000420494.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000241 AC: 6 AN: 248710 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

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: 0.00000684 AC: 10 AN: 1461728 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727170

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.000134 AC: 6 AN: 44704

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111964

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000331 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.84
DANN	Benign	0.79
DEOGEN2	Benign	0.36	T;T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.39	.;.;.;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.045	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N;N;N;N
PhyloP100		-0.51
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.54	N;N;N;N
REVEL	Benign	0.022
Sift	Benign	0.17	T;T;T;T
Sift4G	Benign	0.084	T;T;T;T
Polyphen		0.022	B;B;B;B
Vest4		0.11
MVP		0.18
MPC		0.16
ClinPred		0.0091	T
GERP RS		0.082
Varity_R		0.046
gMVP		0.036
Mutation Taster		=91/9	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

Publications

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Other links and lift over

dbSNP: rs371014575; hg19: chr7-73638366;