6-38923069-T-C

Variant names:

• chr6-38923069-T-C
• rs1160474440
• NM_001206927.2:c.10674T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001206927.2(DNAH8):​c.10674T>C​(p.Asn3558Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000959 in 1,460,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0980
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 6-38923069-T-C is Benign according to our data. Variant chr6-38923069-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 695566.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.098 with no splicing effect.

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.10674T>C	p.Asn3558Asn	synonymous	Exon 72 of 93	NP_001193856.1	A0A075B6F3
	DNAH8	NM_001371.4		c.10023T>C	p.Asn3341Asn	synonymous	Exon 71 of 92	NP_001362.2	Q96JB1-1
	DNAH8-AS1	NR_038401.1		n.782+16A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.10674T>C	p.Asn3558Asn	synonymous	Exon 72 of 93	ENSP00000333363.7	A0A075B6F3
	DNAH8	ENST00000359357.7	TSL:2	c.10023T>C	p.Asn3341Asn	synonymous	Exon 70 of 91	ENSP00000352312.3	Q96JB1-1
	DNAH8	ENST00000449981.6	TSL:5	c.10674T>C	p.Asn3558Asn	synonymous	Exon 71 of 82	ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000959 AC: 14 AN: 1460556 Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8 AN XY: 726496

African (AFR) AF: 0.00 AC: 0 AN: 33422

American (AMR) AF: 0.00 AC: 0 AN: 44460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.00 AC: 0 AN: 85988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111512

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	1.1
DANN	Benign	0.56
PhyloP100		-0.098

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: rs1160474440; hg19: chr6-38890845;