rs190695624

Variant names:

• chr19-50309085-C-T
• rs190695624
• NM_001145809.2:c.5868C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-50309085-C-T
• chr19-50309085-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001145809.2(MYH14):​c.5868C>T​(p.Ala1956Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00892 in 1,613,836 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0091 (82 hom.)
• Consequence: MYH14 NM_001145809.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -3.87
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 19-50309085-C-T is Benign according to our data. Variant chr19-50309085-C-T is described in ClinVar as Benign. ClinVar VariationId is 44076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.87 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00685 (1043/152244) while in subpopulation NFE AF = 0.0108 (733/67996). AF 95% confidence interval is 0.0101. There are 5 homozygotes in GnomAd4. There are 496 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1043 AD gene.

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.5868C>T	p.Ala1956Ala	synonymous	Exon 42 of 43	NP_001139281.1	Q7Z406-2
	MYH14	NM_001077186.2		c.5769C>T	p.Ala1923Ala	synonymous	Exon 41 of 42	NP_001070654.1	Q7Z406-6
	MYH14	NM_024729.4		c.5745C>T	p.Ala1915Ala	synonymous	Exon 40 of 41	NP_079005.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH14	ENST00000642316.2	MANE Select	c.5868C>T	p.Ala1956Ala	synonymous	Exon 42 of 43	ENSP00000493594.1	Q7Z406-2
	MYH14	ENST00000425460.6	TSL:5	c.5769C>T	p.Ala1923Ala	synonymous	Exon 41 of 42	ENSP00000407879.1	Q7Z406-6
	MYH14	ENST00000598205.5	TSL:5	c.5769C>T	p.Ala1923Ala	synonymous	Exon 41 of 42	ENSP00000472543.1	Q7Z406-6

Frequencies

GnomAD3 genomes AF: 0.00686 AC: 1043 AN: 152126 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0186

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.00527

GnomAD2 exomes AF: 0.00782 AC: 1947 AN: 248984 AF XY: 0.00790

Gnomad AFR exome AF: 0.00168

Gnomad AMR exome AF: 0.00330

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.0196

Gnomad NFE exome AF: 0.0108

Gnomad OTH exome AF: 0.00943

GnomAD4 exome AF: 0.00914 AC: 13355 AN: 1461592 Hom.: 82 Cov.: 33 AF XY: 0.00917 AC XY: 6665 AN XY: 727098

African (AFR) AF: 0.00122 AC: 41 AN: 33478

American (AMR) AF: 0.00333 AC: 149 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.000651 AC: 17 AN: 26124

East Asian (EAS) AF: 0.000856 AC: 34 AN: 39698

South Asian (SAS) AF: 0.00357 AC: 308 AN: 86254

European-Finnish (FIN) AF: 0.0199 AC: 1060 AN: 53396

Middle Eastern (MID) AF: 0.00729 AC: 42 AN: 5764

European-Non Finnish (NFE) AF: 0.0101 AC: 11265 AN: 1111800

Other (OTH) AF: 0.00727 AC: 439 AN: 60368

GnomAD4 genome AF: 0.00685 AC: 1043 AN: 152244 Hom.: 5 Cov.: 31 AF XY: 0.00666 AC XY: 496 AN XY: 74432

African (AFR) AF: 0.00128 AC: 53 AN: 41544

American (AMR) AF: 0.00242 AC: 37 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5170

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4830

European-Finnish (FIN) AF: 0.0186 AC: 198 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0108 AC: 733 AN: 67996

Other (OTH) AF: 0.00521 AC: 11 AN: 2110

Alfa AF: 0.00865 Hom.: 5

Bravo AF: 0.00554

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	4	not specified (4)
-	-	1	Autosomal dominant nonsyndromic hearing loss 4A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.21
DANN	Benign	0.94
PhyloP100		-3.9
Mutation Taster		=99/1	polymorphism

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: rs190695624; hg19: chr19-50812342;