rs11012

Variant names:

• chr17-45436075-C-A
• NM_014798.3:c.*1783G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-45436075-C-A
• chr17-45436075-C-G
• chr17-45436075-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014798.3(PLEKHM1):​c.*1783G>T variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLEKHM1 NM_014798.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208

Genes affected

PLEKHM1 (HGNC:29017): (pleckstrin homology and RUN domain containing M1) The protein encoded by this gene is essential for bone resorption, and may play a critical role in vesicular transport in the osteoclast. Mutations in this gene are associated with autosomal recessive osteopetrosis type 6 (OPTB6). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHM1	NM_014798.3	c.*1783G>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000430334.8	NP_055613.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHM1	ENST00000430334	c.*1783G>T		3_prime_UTR_variant	Exon 12 of 12	1	NM_014798.3	ENSP00000389913.3
PLEKHM1	ENST00000579197.5	n.*4514G>T		non_coding_transcript_exon_variant	Exon 11 of 11	2		ENSP00000462282.1
PLEKHM1	ENST00000580404.5	n.2456G>T		non_coding_transcript_exon_variant	Exon 5 of 5	5
PLEKHM1	ENST00000579197.5	n.*4514G>T		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000462282.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.46

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: chr17-43513441;