rs10406788

Variant names:

• chr19-50286710-G-A
• rs10406788
• NM_001145809.2:c.4752+16G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-50286710-G-A
• chr19-50286710-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001145809.2(MYH14):​c.4752+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,556,746 control chromosomes in the GnomAD database, including 9,926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1980 hom., cov: 33)
  • Exomes 𝑓: 0.10 (7946 hom.)
• Consequence: MYH14 NM_001145809.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.76
• Publications: 7 publications found

Genes affected

MYH14 (HGNC:23212): (myosin heavy chain 14) This gene encodes a member of the myosin superfamily. The protein represents a conventional non-muscle myosin; it should not be confused with the unconventional myosin-14 (MYO14). Myosins are actin-dependent motor proteins with diverse functions including regulation of cytokinesis, cell motility, and cell polarity. Mutations in this gene result in one form of autosomal dominant hearing impairment. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

MYH14 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 4A

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 19-50286710-G-A is Benign according to our data. Variant chr19-50286710-G-A is described in ClinVar as Benign. ClinVar VariationId is 257576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145809.2. 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
	MYH14	NM_001145809.2	MANE Select	c.4752+16G>A		intron	N/A	NP_001139281.1	Q7Z406-2
	MYH14	NM_001077186.2		c.4653+16G>A		intron	N/A	NP_001070654.1	Q7Z406-6
	MYH14	NM_024729.4		c.4629+16G>A		intron	N/A	NP_079005.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH14	ENST00000642316.2	MANE Select	c.4752+16G>A		intron	N/A	ENSP00000493594.1	Q7Z406-2
	MYH14	ENST00000425460.6	TSL:5	c.4653+16G>A		intron	N/A	ENSP00000407879.1	Q7Z406-6
	MYH14	ENST00000598205.5	TSL:5	c.4653+16G>A		intron	N/A	ENSP00000472543.1	Q7Z406-6

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21072 AN: 152130 Hom.: 1983 Cov.: 33

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0949

Gnomad ASJ AF: 0.0838

Gnomad EAS AF: 0.0175

Gnomad SAS AF: 0.0558

Gnomad FIN AF: 0.0940

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.135

GnomAD2 exomes AF: 0.0954 AC: 15402 AN: 161446 AF XY: 0.0937

Gnomad AFR exome AF: 0.275

Gnomad AMR exome AF: 0.0672

Gnomad ASJ exome AF: 0.0946

Gnomad EAS exome AF: 0.0137

Gnomad FIN exome AF: 0.0995

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.101

GnomAD4 exome AF: 0.101 AC: 141435 AN: 1404498 Hom.: 7946 Cov.: 31 AF XY: 0.0987 AC XY: 68487 AN XY: 693546

African (AFR) AF: 0.262 AC: 8385 AN: 32016

American (AMR) AF: 0.0698 AC: 2525 AN: 36172

Ashkenazi Jewish (ASJ) AF: 0.0938 AC: 2370 AN: 25270

East Asian (EAS) AF: 0.0146 AC: 532 AN: 36414

South Asian (SAS) AF: 0.0516 AC: 4114 AN: 79664

European-Finnish (FIN) AF: 0.0997 AC: 4946 AN: 49598

Middle Eastern (MID) AF: 0.117 AC: 482 AN: 4114

European-Non Finnish (NFE) AF: 0.103 AC: 111878 AN: 1083040

Other (OTH) AF: 0.107 AC: 6203 AN: 58210

GnomAD4 genome AF: 0.138 AC: 21086 AN: 152248 Hom.: 1980 Cov.: 33 AF XY: 0.135 AC XY: 10047 AN XY: 74446

African (AFR) AF: 0.259 AC: 10754 AN: 41528

American (AMR) AF: 0.0948 AC: 1450 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0838 AC: 291 AN: 3472

East Asian (EAS) AF: 0.0170 AC: 88 AN: 5176

South Asian (SAS) AF: 0.0563 AC: 272 AN: 4832

European-Finnish (FIN) AF: 0.0940 AC: 998 AN: 10614

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6841 AN: 68010

Other (OTH) AF: 0.133 AC: 281 AN: 2112

Alfa AF: 0.114 Hom.: 1554

Bravo AF: 0.144

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.14
DANN	Benign	0.85
PhyloP100		-2.8
Mutation Taster		=100/0	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: rs10406788; hg19: chr19-50789967;