17-75620008-T-G

Variant names:

• chr17-75620008-T-G
• rs820152
• NM_001395058.1:c.7431T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395058.1(MYO15B):​c.7431T>G​(p.Asn2477Lys) 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. 8/10 in silico tools predict 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: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYO15B NM_001395058.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706
• Publications: 19 publications found

Genes affected

MYO15B (HGNC:14083): (myosin XVB) Predicted to enable ATP binding activity; actin binding activity; and cytoskeletal motor activity. Predicted to be located in brush border; cytoplasm; and cytoskeleton. Predicted to be part of myosin complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.10513228).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO15B	NM_001395058.1	c.7431T>G	p.Asn2477Lys	missense_variant	Exon 47 of 64	ENST00000645453.3	NP_001381987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO15B	ENST00000645453.3	c.7431T>G	p.Asn2477Lys	missense_variant	Exon 47 of 64		NM_001395058.1	ENSP00000495242.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 549404 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 297390

African (AFR) AF: 0.00 AC: 0 AN: 15796

American (AMR) AF: 0.00 AC: 0 AN: 34602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19908

East Asian (EAS) AF: 0.00 AC: 0 AN: 32094

South Asian (SAS) AF: 0.00 AC: 0 AN: 62570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4066

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 316306

Other (OTH) AF: 0.00 AC: 0 AN: 30552

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 9783

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.70
DANN	Benign	0.56
DEOGEN2	Benign	0.0082	T;T;.
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.46	T;T;T
MetaRNN	Benign	0.11	T;T;T
PhyloP100		-0.71
Sift4G	Benign	0.070	T;T;.
Vest4		0.12
GERP RS		-7.4
PromoterAI		0.018	Neutral
Varity_R		0.079

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: rs820152; hg19: chr17-73616088;