chr16-21019643-G-A

Variant names:

• chr16-21019643-G-A
• rs148237228
• NM_001347886.2:c.5865C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001347886.2(DNAH3):​c.5865C>T​(p.Asn1955Asn) variant causes a synonymous change. The variant allele was found at a frequency of 0.00816 in 1,614,060 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (3 hom., cov: 30)
  • Exomes 𝑓: 0.0084 (76 hom.)
• Consequence: DNAH3 NM_001347886.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.74
• Publications: 2 publications found

Genes affected

DNAH3 (HGNC:2949): (dynein axonemal heavy chain 3) This gene belongs to the dynein family, whose members encode large proteins that are constituents of the microtubule-associated motor protein complex. This complex is composed of dynein heavy, intermediate and light chains, which can be axonemal or cytoplasmic. This protein is an axonemal dynein heavy chain. It is involved in producing force for ciliary beating by using energy from ATP hydrolysis. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Dec 2016]

DNAH3 Gene-Disease associations (from GenCC):

• male infertility

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 16-21019643-G-A is Benign according to our data. Variant chr16-21019643-G-A is described in ClinVar as Benign. ClinVar VariationId is 402722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347886.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH3	NM_001347886.2	MANE Select	c.5865C>T	p.Asn1955Asn	synonymous	Exon 41 of 62	NP_001334815.1
	DNAH3	NM_017539.2		c.6003C>T	p.Asn2001Asn	synonymous	Exon 41 of 62	NP_060009.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH3	ENST00000698260.1	MANE Select	c.5865C>T	p.Asn1955Asn	synonymous	Exon 41 of 62	ENSP00000513632.1
	DNAH3	ENST00000261383.3	TSL:1	c.6003C>T	p.Asn2001Asn	synonymous	Exon 41 of 62	ENSP00000261383.3
	DNAH3	ENST00000572931.1	TSL:1	n.1155C>T		non_coding_transcript_exon	Exon 8 of 8

Frequencies

GnomAD3 genomes AF: 0.00626 AC: 953 AN: 152130 Hom.: 3 Cov.: 30

Gnomad AFR AF: 0.00198

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000943

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00964

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00561 AC: 1409 AN: 251346 AF XY: 0.00578

Gnomad AFR exome AF: 0.00240

Gnomad AMR exome AF: 0.00562

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000971

Gnomad NFE exome AF: 0.00952

Gnomad OTH exome AF: 0.00782

GnomAD4 exome AF: 0.00836 AC: 12215 AN: 1461812 Hom.: 76 Cov.: 31 AF XY: 0.00808 AC XY: 5877 AN XY: 727208

African (AFR) AF: 0.00194 AC: 65 AN: 33478

American (AMR) AF: 0.00579 AC: 259 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00176 AC: 46 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000383 AC: 33 AN: 86256

European-Finnish (FIN) AF: 0.00107 AC: 57 AN: 53420

Middle Eastern (MID) AF: 0.0158 AC: 91 AN: 5768

European-Non Finnish (NFE) AF: 0.0101 AC: 11193 AN: 1111944

Other (OTH) AF: 0.00780 AC: 471 AN: 60396

GnomAD4 genome AF: 0.00626 AC: 953 AN: 152248 Hom.: 3 Cov.: 30 AF XY: 0.00595 AC XY: 443 AN XY: 74434

African (AFR) AF: 0.00197 AC: 82 AN: 41558

American (AMR) AF: 0.0111 AC: 169 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.000943 AC: 10 AN: 10604

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00965 AC: 656 AN: 68014

Other (OTH) AF: 0.00758 AC: 16 AN: 2112

Alfa AF: 0.00725 Hom.: 0

Bravo AF: 0.00695

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0104

EpiControl AF: 0.0111

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jul 20, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.2
DANN	Benign	0.55
PhyloP100		4.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs148237228; hg19: chr16-21030965;