5-138869248-T-C

Variant names:

• chr5-138869248-T-C
• rs188837597
• NM_015564.3:c.*3762A>G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_015564.3(LRRTM2):​c.*3762A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000826 in 151,400 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.00083 (0 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: LRRTM2 NM_015564.3 3_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.89

Genes affected

LRRTM2 (HGNC:19409): (leucine rich repeat transmembrane neuronal 2) Predicted to enable neurexin family protein binding activity. Predicted to be involved in regulation of postsynaptic density assembly. Predicted to act upstream of or within several processes, including long-term synaptic potentiation; negative regulation of receptor internalization; and positive regulation of synapse assembly. Is active in GABA-ergic synapse. Is integral component of postsynaptic specialization membrane. [provided by Alliance of Genome Resources, Apr 2022]

CTNNA1 (HGNC:2509): (catenin alpha 1) This gene encodes a member of the catenin family of proteins that play an important role in cell adhesion process by connecting cadherins located on the plasma membrane to the actin filaments inside the cell. The encoded mechanosensing protein contains three vinculin homology domains and undergoes conformational changes in response to cytoskeletal tension, resulting in the reconfiguration of cadherin-actin filament connections. Certain mutations in this gene cause butterfly-shaped pigment dystrophy. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 5-138869248-T-C is Benign according to our data. Variant chr5-138869248-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 223765.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 125 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRTM2	NM_015564.3	c.*3762A>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000274711.7	NP_056379.1
CTNNA1	NM_001903.5	c.1063-16964T>C		intron_variant	Intron 7 of 17	ENST00000302763.12	NP_001894.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRTM2	ENST00000274711	c.*3762A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_015564.3	ENSP00000274711.5
CTNNA1	ENST00000302763.12	c.1063-16964T>C		intron_variant	Intron 7 of 17	1	NM_001903.5	ENSP00000304669.7

Frequencies

GnomAD3 genomes AF: 0.000826 AC: 125 AN: 151318 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000364

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.000460

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000975

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.000480

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.000826 AC: 125 AN: 151400 Hom.: 0 Cov.: 31 AF XY: 0.000798 AC XY: 59 AN XY: 73956

Gnomad4 AFR AF: 0.000363

Gnomad4 AMR AF: 0.000460

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000975

Gnomad4 NFE AF: 0.00125

Gnomad4 OTH AF: 0.000477

Alfa AF: 0.00132 Hom.: 0

Bravo AF: 0.000850

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Hereditary cancer-predisposing syndrome Benign:1

Dec 01, 2015

University of Washington Department of Laboratory Medicine, University of Washington

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.81

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

LitVar

Other links and lift over

dbSNP: rs188837597; hg19: chr5-138204937;