1-30757682-T-C

Variant names:

• chr1-30757682-T-C
• NM_006762.3:c.64A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006762.3(LAPTM5):​c.64A>G​(p.Thr22Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,538 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LAPTM5 NM_006762.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.01

Genes affected

LAPTM5 (HGNC:29612): (lysosomal protein transmembrane 5) This gene encodes a transmembrane receptor that is associated with lysosomes. The encoded protein, also known as E3 protein, may play a role in hematopoiesis. [provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAPTM5	NM_006762.3	c.64A>G	p.Thr22Ala	missense_variant	Exon 1 of 8	ENST00000294507.4	NP_006753.1
LAPTM5	XM_011542098.3	c.64A>G	p.Thr22Ala	missense_variant	Exon 1 of 6		XP_011540400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAPTM5	ENST00000294507.4	c.64A>G	p.Thr22Ala	missense_variant	Exon 1 of 8	1	NM_006762.3	ENSP00000294507.3
LAPTM5	ENST00000476492.1	n.76A>G		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461538 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727040

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.64A>G (p.T22A) alteration is located in exon 1 (coding exon 1) of the LAPTM5 gene. This alteration results from a A to G substitution at nucleotide position 64, causing the threonine (T) at amino acid position 22 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0039	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.040
Sift	Benign	0.20	T
Sift4G	Benign	0.61	T
Polyphen		0.049	B
Vest4		0.54
MutPred		0.32		Loss of glycosylation at T22 (P = 0.1887);
MVP		0.49
MPC		0.20
ClinPred		0.15	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.088
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-31230529;