rs181567755

Variant names:

• chr19-50309670-G-A
• rs181567755
• NM_001145809.2:c.5991G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-50309670-G-A
• chr19-50309670-G-C
• chr19-50309670-G-T

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.5991G>A​(p.Thr1997Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,485,222 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00082 (1 hom., cov: 30)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: MYH14 NM_001145809.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -9.18
• Publications: 0 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=-0.89).
• BP6: Variant 19-50309670-G-A is Benign according to our data. Variant chr19-50309670-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 164208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-9.18 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000817 (118/144380) while in subpopulation AFR AF = 0.00284 (111/39108). AF 95% confidence interval is 0.00241. There are 1 homozygotes in GnomAd4. There are 57 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 118 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.5991G>A	p.Thr1997Thr	synonymous	Exon 43 of 43	NP_001139281.1	Q7Z406-2
	MYH14	NM_001077186.2		c.5892G>A	p.Thr1964Thr	synonymous	Exon 42 of 42	NP_001070654.1	Q7Z406-6
	MYH14	NM_024729.4		c.5868G>A	p.Thr1956Thr	synonymous	Exon 41 of 41	NP_079005.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH14	ENST00000642316.2	MANE Select	c.5991G>A	p.Thr1997Thr	synonymous	Exon 43 of 43	ENSP00000493594.1	Q7Z406-2
	MYH14	ENST00000425460.6	TSL:5	c.5892G>A	p.Thr1964Thr	synonymous	Exon 42 of 42	ENSP00000407879.1	Q7Z406-6
	MYH14	ENST00000598205.5	TSL:5	c.5892G>A	p.Thr1964Thr	synonymous	Exon 42 of 42	ENSP00000472543.1	Q7Z406-6

Frequencies

GnomAD3 genomes AF: 0.000804 AC: 116 AN: 144276 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00279

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000281

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000451

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000265 AC: 64 AN: 241476 AF XY: 0.000251

Gnomad AFR exome AF: 0.00328

Gnomad AMR exome AF: 0.0000883

Gnomad ASJ exome AF: 0.000303

Gnomad EAS exome AF: 0.000114

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000459

Gnomad OTH exome AF: 0.000170

GnomAD4 exome AF: 0.000144 AC: 193 AN: 1340842 Hom.: 0 Cov.: 35 AF XY: 0.000129 AC XY: 86 AN XY: 664868

African (AFR) AF: 0.00350 AC: 105 AN: 29998

American (AMR) AF: 0.0000739 AC: 3 AN: 40572

Ashkenazi Jewish (ASJ) AF: 0.000138 AC: 3 AN: 21736

East Asian (EAS) AF: 0.000261 AC: 8 AN: 30598

South Asian (SAS) AF: 0.0000475 AC: 4 AN: 84270

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41080

Middle Eastern (MID) AF: 0.000195 AC: 1 AN: 5132

European-Non Finnish (NFE) AF: 0.0000570 AC: 59 AN: 1035210

Other (OTH) AF: 0.000191 AC: 10 AN: 52246

GnomAD4 genome AF: 0.000817 AC: 118 AN: 144380 Hom.: 1 Cov.: 30 AF XY: 0.000813 AC XY: 57 AN XY: 70120

African (AFR) AF: 0.00284 AC: 111 AN: 39108

American (AMR) AF: 0.000280 AC: 4 AN: 14286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3402

East Asian (EAS) AF: 0.00 AC: 0 AN: 4422

South Asian (SAS) AF: 0.00 AC: 0 AN: 4180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.0000451 AC: 3 AN: 66470

Other (OTH) AF: 0.00 AC: 0 AN: 2038

Alfa AF: 0.000229 Hom.: 0

Bravo AF: 0.000812

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.045
DANN	Benign	0.94
PhyloP100		-9.2
Mutation Taster		=100/0	polymorphism

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: rs181567755; hg19: chr19-50812927;