1-30742517-T-C

Variant names:

• chr1-30742517-T-C
• rs1050663
• NM_006762.3:c.120A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006762.3(LAPTM5):​c.120A>G​(p.Ser40Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,612,044 control chromosomes in the GnomAD database, including 217,685 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.55 (23304 hom., cov: 32)
  • Exomes 𝑓: 0.51 (194381 hom.)
• Consequence: LAPTM5 NM_006762.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.21
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-5.21 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006762.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAPTM5	NM_006762.3	MANE Select	c.120A>G	p.Ser40Ser	synonymous	Exon 2 of 8	NP_006753.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAPTM5	ENST00000294507.4	TSL:1 MANE Select	c.120A>G	p.Ser40Ser	synonymous	Exon 2 of 8	ENSP00000294507.3
	LAPTM5	ENST00000464569.1	TSL:5	n.345A>G		non_coding_transcript_exon	Exon 2 of 8
	LAPTM5	ENST00000476492.1	TSL:2	n.132A>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83528 AN: 151942 Hom.: 23273 Cov.: 32

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.542

GnomAD2 exomes AF: 0.556 AC: 138954 AN: 249732 AF XY: 0.547

Gnomad AFR exome AF: 0.603

Gnomad AMR exome AF: 0.729

Gnomad ASJ exome AF: 0.483

Gnomad EAS exome AF: 0.693

Gnomad FIN exome AF: 0.583

Gnomad NFE exome AF: 0.483

Gnomad OTH exome AF: 0.527

GnomAD4 exome AF: 0.511 AC: 746647 AN: 1459984 Hom.: 194381 Cov.: 41 AF XY: 0.511 AC XY: 371022 AN XY: 726274

African (AFR) AF: 0.602 AC: 20161 AN: 33468

American (AMR) AF: 0.719 AC: 32114 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 12494 AN: 26110

East Asian (EAS) AF: 0.722 AC: 28639 AN: 39668

South Asian (SAS) AF: 0.539 AC: 46433 AN: 86140

European-Finnish (FIN) AF: 0.569 AC: 30180 AN: 53080

Middle Eastern (MID) AF: 0.528 AC: 3047 AN: 5768

European-Non Finnish (NFE) AF: 0.488 AC: 542018 AN: 1110764

Other (OTH) AF: 0.523 AC: 31561 AN: 60350

GnomAD4 genome AF: 0.550 AC: 83607 AN: 152060 Hom.: 23304 Cov.: 32 AF XY: 0.555 AC XY: 41272 AN XY: 74346

African (AFR) AF: 0.600 AC: 24878 AN: 41448

American (AMR) AF: 0.647 AC: 9888 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1661 AN: 3464

East Asian (EAS) AF: 0.683 AC: 3535 AN: 5172

South Asian (SAS) AF: 0.528 AC: 2547 AN: 4822

European-Finnish (FIN) AF: 0.584 AC: 6186 AN: 10592

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33182 AN: 67956

Other (OTH) AF: 0.546 AC: 1152 AN: 2110

Alfa AF: 0.511 Hom.: 41744

Bravo AF: 0.561

Asia WGS AF: 0.620 AC: 2155 AN: 3478

EpiCase AF: 0.488

EpiControl AF: 0.487

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.36
PhyloP100		-5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs1050663; hg19: chr1-31215364; COSMIC: COSV99612686; COSMIC: COSV99612686;