rs114401631

Variant names:

• chr6-38929576-C-G
• rs114401631
• NM_001206927.2:c.11184C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-38929576-C-G
• chr6-38929576-C-T
• chr6-38929576-C-A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS1

The NM_001206927.2(DNAH8):​c.11184C>G​(p.Pro3728Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000696 in 1,612,532 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 (★★). Synonymous variant affecting the same amino acid position (i.e. P3728P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00059 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00071 (1 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.981
• Publications: 1 publications found

Genes affected

DNAH8 (HGNC:2952): (dynein axonemal heavy chain 8) The protein encoded by this gene is a heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility. Axonemal dyneins generate force through hydrolysis of ATP and binding to microtubules. [provided by RefSeq, Jan 2012]

DNAH8-AS1 (HGNC:40188): (DNAH8 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 6-38929576-C-G is Benign according to our data. Variant chr6-38929576-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 414431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.981 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000594 (90/151550) while in subpopulation AMR AF = 0.00118 (18/15210). AF 95% confidence interval is 0.000764. There are 0 homozygotes in GnomAd4. There are 42 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206927.2. 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
	DNAH8	NM_001206927.2	MANE Select	c.11184C>G	p.Pro3728Pro	synonymous	Exon 75 of 93	NP_001193856.1	A0A075B6F3
	DNAH8	NM_001371.4		c.10533C>G	p.Pro3511Pro	synonymous	Exon 74 of 92	NP_001362.2	Q96JB1-1
	DNAH8-AS1	NR_038401.1		n.161-4525G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.11184C>G	p.Pro3728Pro	synonymous	Exon 75 of 93	ENSP00000333363.7	A0A075B6F3
	DNAH8	ENST00000359357.7	TSL:2	c.10533C>G	p.Pro3511Pro	synonymous	Exon 73 of 91	ENSP00000352312.3	Q96JB1-1
	DNAH8	ENST00000449981.6	TSL:5	c.11184C>G	p.Pro3728Pro	synonymous	Exon 74 of 82	ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes AF: 0.000594 AC: 90 AN: 151434 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000192

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000869

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000494 AC: 124 AN: 250872 AF XY: 0.000546

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.000838

Gnomad OTH exome AF: 0.000818

GnomAD4 exome AF: 0.000706 AC: 1032 AN: 1460982 Hom.: 1 Cov.: 31 AF XY: 0.000706 AC XY: 513 AN XY: 726768

African (AFR) AF: 0.0000598 AC: 2 AN: 33442

American (AMR) AF: 0.000559 AC: 25 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86178

European-Finnish (FIN) AF: 0.000244 AC: 13 AN: 53274

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5760

European-Non Finnish (NFE) AF: 0.000858 AC: 954 AN: 1111490

Other (OTH) AF: 0.000563 AC: 34 AN: 60354

GnomAD4 genome AF: 0.000594 AC: 90 AN: 151550 Hom.: 0 Cov.: 31 AF XY: 0.000567 AC XY: 42 AN XY: 74064

African (AFR) AF: 0.000242 AC: 10 AN: 41356

American (AMR) AF: 0.00118 AC: 18 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.000192 AC: 2 AN: 10404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000869 AC: 59 AN: 67862

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.000650 Hom.: 1

Bravo AF: 0.000608

EpiCase AF: 0.00137

EpiControl AF: 0.000889

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	DNAH8-related disorder (1)
-	-	1	not provided (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	4.1
DANN	Benign	0.71
PhyloP100		-0.98
Mutation Taster		=100/0	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: rs114401631; hg19: chr6-38897352;