13-109009011-C-G

Variant names:

• chr13-109009011-C-G
• rs3825491
• NM_001198950.3:c.2557C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001198950.3(MYO16):​c.2557C>G​(p.Pro853Ala) variant causes a missense change. The variant allele was found at a frequency of 0.393 in 1,598,464 control chromosomes in the GnomAD database, including 126,969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.39 (11736 hom., cov: 32)
  • Exomes 𝑓: 0.39 (115233 hom.)
• Consequence: MYO16 NM_001198950.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.92
• Publications: 21 publications found

Genes affected

MYO16 (HGNC:29822): (myosin XVI) This gene encodes an unconventional myosin protein. The encoded protein has been proposed to act as a serine/threonine phosphatase-1 targeting or regulatory subunit. Studies in a rat cell line suggest that this protein may regulate cell cycle progression. A variant within this gene may be associated with susceptibility to schizophrenia and elevated expression of this gene has been observed in the frontal cortex of human schizophrenia patients. [provided by RefSeq, Mar 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=9.509407E-5).
• BP6: Variant 13-109009011-C-G is Benign according to our data. Variant chr13-109009011-C-G is described in ClinVar as Benign. ClinVar VariationId is 3059068.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198950.3. 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
	MYO16	NM_001198950.3	MANE Select	c.2557C>G	p.Pro853Ala	missense	Exon 22 of 35	NP_001185879.1
	MYO16	NM_015011.3		c.2491C>G	p.Pro831Ala	missense	Exon 22 of 35	NP_055826.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO16	ENST00000457511.7	TSL:1 MANE Select	c.2557C>G	p.Pro853Ala	missense	Exon 22 of 35	ENSP00000401633.3
	MYO16	ENST00000356711.7	TSL:1	c.2491C>G	p.Pro831Ala	missense	Exon 22 of 35	ENSP00000349145.2
	MYO16	ENST00000251041.10	TSL:5	c.2491C>G	p.Pro831Ala	missense	Exon 22 of 25	ENSP00000251041.5

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58816 AN: 151904 Hom.: 11730 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.351

GnomAD2 exomes AF: 0.435 AC: 105227 AN: 242026 AF XY: 0.435

Gnomad AFR exome AF: 0.337

Gnomad AMR exome AF: 0.486

Gnomad ASJ exome AF: 0.445

Gnomad EAS exome AF: 0.668

Gnomad FIN exome AF: 0.453

Gnomad NFE exome AF: 0.375

Gnomad OTH exome AF: 0.394

GnomAD4 exome AF: 0.393 AC: 568933 AN: 1446442 Hom.: 115233 Cov.: 35 AF XY: 0.396 AC XY: 285037 AN XY: 719058

African (AFR) AF: 0.329 AC: 10809 AN: 32894

American (AMR) AF: 0.474 AC: 19657 AN: 41464

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 11367 AN: 25772

East Asian (EAS) AF: 0.633 AC: 24969 AN: 39442

South Asian (SAS) AF: 0.513 AC: 42359 AN: 82640

European-Finnish (FIN) AF: 0.445 AC: 23709 AN: 53268

Middle Eastern (MID) AF: 0.393 AC: 2253 AN: 5730

European-Non Finnish (NFE) AF: 0.371 AC: 409964 AN: 1105338

Other (OTH) AF: 0.398 AC: 23846 AN: 59894

GnomAD4 genome AF: 0.387 AC: 58840 AN: 152022 Hom.: 11736 Cov.: 32 AF XY: 0.396 AC XY: 29432 AN XY: 74306

African (AFR) AF: 0.332 AC: 13780 AN: 41474

American (AMR) AF: 0.409 AC: 6253 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1550 AN: 3472

East Asian (EAS) AF: 0.659 AC: 3408 AN: 5170

South Asian (SAS) AF: 0.511 AC: 2464 AN: 4826

European-Finnish (FIN) AF: 0.460 AC: 4859 AN: 10552

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25334 AN: 67940

Other (OTH) AF: 0.349 AC: 736 AN: 2108

Alfa AF: 0.368 Hom.: 7878

Bravo AF: 0.380

TwinsUK AF: 0.371 AC: 1377

ALSPAC AF: 0.381 AC: 1467

ESP6500AA AF: 0.340 AC: 1496

ESP6500EA AF: 0.376 AC: 3231

ExAC AF: 0.431 AC: 52323

Asia WGS AF: 0.558 AC: 1941 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MYO16-related disorder Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Benign	0.91
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
MetaRNN	Benign	0.000095	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.9
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.44
Sift	Benign	0.20	T
Sift4G	Benign	0.13	T
Polyphen		0.97	D
Vest4		0.088
MPC		0.54
ClinPred		0.029	T
GERP RS		5.7
Varity_R		0.22
gMVP		0.32
Mutation Taster		=94/6	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: rs3825491; hg19: chr13-109661359; COSMIC: COSV107229935;