17-75596531-C-T

Variant names:

• chr17-75596531-C-T
• rs72854930
• NM_001395058.1:c.3369C>T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001395058.1(MYO15B):​c.3369C>T​(p.Ser1123Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00325 in 703,012 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (2 hom., cov: 34)
  • Exomes 𝑓: 0.0034 (1 hom.)
• Consequence: MYO15B NM_001395058.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.464

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

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004033953).
• BP6: Variant 17-75596531-C-T is Benign according to our data. Variant chr17-75596531-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2648270.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.464 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO15B	NM_001395058.1	c.3369C>T	p.Ser1123Ser	synonymous_variant	Exon 13 of 64	ENST00000645453.3	NP_001381987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO15B	ENST00000645453.3	c.3369C>T	p.Ser1123Ser	synonymous_variant	Exon 13 of 64		NM_001395058.1	ENSP00000495242.3

Frequencies

GnomAD3 genomes AF: 0.00284 AC: 432 AN: 152262 Hom.: 2 Cov.: 34

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00497

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00269 AC: 369 AN: 137034 Hom.: 1 AF XY: 0.00239 AC XY: 178 AN XY: 74404

Gnomad AFR exome AF: 0.000931

Gnomad AMR exome AF: 0.00184

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00129

Gnomad NFE exome AF: 0.00543

Gnomad OTH exome AF: 0.00264

GnomAD4 exome AF: 0.00337 AC: 1854 AN: 550632 Hom.: 1 Cov.: 0 AF XY: 0.00316 AC XY: 942 AN XY: 298096

Gnomad4 AFR exome AF: 0.000949

Gnomad4 AMR exome AF: 0.00170

Gnomad4 ASJ exome AF: 0.0000499

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00122

Gnomad4 NFE exome AF: 0.00522

Gnomad4 OTH exome AF: 0.00271

GnomAD4 genome AF: 0.00284 AC: 432 AN: 152380 Hom.: 2 Cov.: 34 AF XY: 0.00268 AC XY: 200 AN XY: 74514

Gnomad4 AFR AF: 0.000769

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.00497

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00359 Hom.: 0

Bravo AF: 0.00290

TwinsUK AF: 0.00431 AC: 16

ALSPAC AF: 0.00467 AC: 18

ExAC AF: 0.00105 AC: 21

Asia WGS AF: 0.000289 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MYO15B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_noAF	Benign	-0.48
CADD	Benign	4.1
DANN	Benign	0.86
DEOGEN2	Benign	0.0067	T
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.0040	T
Sift4G	Pathogenic	0.0	D
Vest4		0.35
GERP RS		0.67
Varity_R		0.037

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: rs72854930; hg19: chr17-73592612;