7-74216066-C-T

Variant names:

• chr7-74216066-C-T
• NM_032464.3:c.91C>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.91C>T​(p.Pro31Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LAT2 NM_032464.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.134
• 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=0.19129395).

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.91C>T	p.Pro31Ser	missense	Exon 3 of 14	NP_115853.2	Q9GZY6-1
	LAT2	NM_014146.4		c.91C>T	p.Pro31Ser	missense	Exon 2 of 13	NP_054865.2
	LAT2	NM_032463.3		c.91C>T	p.Pro31Ser	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.91C>T	p.Pro31Ser	missense	Exon 3 of 14	ENSP00000420494.1	Q9GZY6-1
	LAT2	ENST00000275635.11	TSL:1	c.91C>T	p.Pro31Ser	missense	Exon 3 of 14	ENSP00000275635.7	Q9GZY6-1
	LAT2	ENST00000344995.9	TSL:1	c.91C>T	p.Pro31Ser	missense	Exon 2 of 13	ENSP00000344881.5	Q9GZY6-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.15
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.96
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.94	L
PhyloP100		0.13
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-7.9	D
REVEL	Benign	0.063
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.71	P
Vest4		0.22
MutPred		0.28		Gain of MoRF binding (P = 0.0537)
MVP		0.14
MPC		0.18
ClinPred		0.32	T
GERP RS		-0.57
Varity_R		0.12
gMVP		0.18
Mutation Taster		=92/8	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

hg19: chr7-73630396;