rs2955379

Variant names:

• chr17-18149553-T-C
• rs2955379
• NM_016239.4:c.7185T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-18149553-T-C
• chr17-18149553-T-A
• chr17-18149553-T-G

Variant summary

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

The NM_016239.4(MYO15A):​c.7185T>C​(p.Phe2395Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,614,224 control chromosomes in the GnomAD database, including 802,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (75405 hom., cov: 33)
  • Exomes 𝑓: 1.0 (726636 hom.)
• Consequence: MYO15A NM_016239.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.603
• Publications: 20 publications found

Genes affected

MYO15A (HGNC:7594): (myosin XVA) This gene encodes an unconventional myosin. This protein differs from other myosins in that it has a long N-terminal extension preceding the conserved motor domain. Studies in mice suggest that this protein is necessary for actin organization in the hair cells of the cochlea. Mutations in this gene have been associated with profound, congenital, neurosensory, nonsyndromal deafness. This gene is located within the Smith-Magenis syndrome region on chromosome 17. Read-through transcripts containing an upstream gene and this gene have been identified, but they are not thought to encode a fusion protein. Several alternatively spliced transcript variants have been described, but their full length sequences have not been determined. [provided by RefSeq, Jul 2008]

MYO15A Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC124903944 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 17-18149553-T-C is Benign according to our data. Variant chr17-18149553-T-C is described in ClinVar as Benign. ClinVar VariationId is 45758.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.603 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016239.4. 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
	MYO15A	NM_016239.4	MANE Select	c.7185T>C	p.Phe2395Phe	synonymous	Exon 35 of 66	NP_057323.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO15A	ENST00000647165.2	MANE Select	c.7185T>C	p.Phe2395Phe	synonymous	Exon 35 of 66	ENSP00000495481.1	Q9UKN7-1
	MYO15A	ENST00000578999.1	TSL:5	n.806T>C		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.995 AC: 151427 AN: 152238 Hom.: 75341 Cov.: 33

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.950

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.984

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.998

GnomAD2 exomes AF: 0.986 AC: 246159 AN: 249576 AF XY: 0.990

Gnomad AFR exome AF: 1.00

Gnomad AMR exome AF: 0.904

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.991

GnomAD4 exome AF: 0.997 AC: 1457389 AN: 1461868 Hom.: 726636 Cov.: 69 AF XY: 0.997 AC XY: 725343 AN XY: 727236

African (AFR) AF: 1.00 AC: 33468 AN: 33480

American (AMR) AF: 0.911 AC: 40739 AN: 44724

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26135 AN: 26136

East Asian (EAS) AF: 0.999 AC: 39666 AN: 39700

South Asian (SAS) AF: 1.00 AC: 86234 AN: 86258

European-Finnish (FIN) AF: 1.00 AC: 53409 AN: 53410

Middle Eastern (MID) AF: 0.996 AC: 5745 AN: 5766

European-Non Finnish (NFE) AF: 1.00 AC: 1111715 AN: 1112002

Other (OTH) AF: 0.998 AC: 60278 AN: 60392

GnomAD4 genome AF: 0.995 AC: 151550 AN: 152356 Hom.: 75405 Cov.: 33 AF XY: 0.994 AC XY: 74029 AN XY: 74504

African (AFR) AF: 1.00 AC: 41550 AN: 41566

American (AMR) AF: 0.951 AC: 14551 AN: 15308

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5186

South Asian (SAS) AF: 1.00 AC: 4831 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10628 AN: 10628

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68022 AN: 68044

Other (OTH) AF: 0.998 AC: 2110 AN: 2114

Alfa AF: 0.998 Hom.: 39601

Bravo AF: 0.990

Asia WGS AF: 0.998 AC: 3470 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 1.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	Autosomal recessive nonsyndromic hearing loss 3 (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.0
DANN	Benign	0.78
PhyloP100		-0.60
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2955379; hg19: chr17-18052867; COSMIC: COSV52761979; COSMIC: COSV52761979;