13-108666025-C-T

Variant names:

• chr13-108666025-C-T
• rs61745206
• NM_001198950.3:c.168C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001198950.3(MYO16):​c.168C>T​(p.Arg56Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00561 in 1,614,012 control chromosomes in the GnomAD database, including 378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (210 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (168 hom.)
• Consequence: MYO16 NM_001198950.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.07
• Publications: 4 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 13-108666025-C-T is Benign according to our data. Variant chr13-108666025-C-T is described in ClinVar as Benign. ClinVar VariationId is 785448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.07 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0981 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO16	NM_001198950.3	MANE Select	c.168C>T	p.Arg56Arg	synonymous	Exon 2 of 35	NP_001185879.1	F8W883
	MYO16	NM_015011.3		c.102C>T	p.Arg34Arg	synonymous	Exon 2 of 35	NP_055826.1	Q9Y6X6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO16	ENST00000457511.7	TSL:1 MANE Select	c.168C>T	p.Arg56Arg	synonymous	Exon 2 of 35	ENSP00000401633.3	F8W883
	MYO16	ENST00000356711.7	TSL:1	c.102C>T	p.Arg34Arg	synonymous	Exon 2 of 35	ENSP00000349145.2	Q9Y6X6-1
	MYO16	ENST00000251041.10	TSL:5	c.102C>T	p.Arg34Arg	synonymous	Exon 2 of 25	ENSP00000251041.5	Q9Y6X6-3

Frequencies

GnomAD3 genomes AF: 0.0290 AC: 4413 AN: 152082 Hom.: 210 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00982

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0186

GnomAD2 exomes AF: 0.00777 AC: 1952 AN: 251062 AF XY: 0.00567

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.00396

Gnomad ASJ exome AF: 0.00626

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000476

Gnomad OTH exome AF: 0.00441

GnomAD4 exome AF: 0.00317 AC: 4635 AN: 1461814 Hom.: 168 Cov.: 31 AF XY: 0.00282 AC XY: 2049 AN XY: 727208

African (AFR) AF: 0.104 AC: 3478 AN: 33476

American (AMR) AF: 0.00459 AC: 205 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00639 AC: 167 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000290 AC: 25 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5768

European-Non Finnish (NFE) AF: 0.000317 AC: 353 AN: 1111960

Other (OTH) AF: 0.00647 AC: 391 AN: 60394

GnomAD4 genome AF: 0.0290 AC: 4419 AN: 152198 Hom.: 210 Cov.: 32 AF XY: 0.0275 AC XY: 2049 AN XY: 74406

African (AFR) AF: 0.101 AC: 4175 AN: 41492

American (AMR) AF: 0.00981 AC: 150 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00547 AC: 19 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68022

Other (OTH) AF: 0.0184 AC: 39 AN: 2116

Alfa AF: 0.0138 Hom.: 54

Bravo AF: 0.0325

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000711

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.46
DANN	Benign	0.65
PhyloP100		-1.1
Mutation Taster		=97/3	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: rs61745206; hg19: chr13-109318373; COSMIC: COSV51781559;