rs1553641484

Positions:

• chr3-52388800-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000420323.7(DNAH1):​c.9364-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DNAH1 ENST00000420323.7 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0002973
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.60

Genes affected

DNAH1 (HGNC:2940): (dynein axonemal heavy chain 1) This gene encodes an inner dynein arm heavy chain that provides structural support between the radial spokes and the outer doublet of the sperm tail. Naturally occurring mutations in this gene are associated with primary ciliary dyskinesia and multiple morphological anomalies of the flagella that result in asthenozoospermia and male infertility. Mice with a homozygous knockout of the orthologous gene are viable but have reduced sperm motility and are infertile. [provided by RefSeq, Feb 2017]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-52388800-C-T is Benign according to our data. Variant chr3-52388800-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 544644.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH1	NM_015512.5	c.9364-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000420323.7	NP_056327.4
DNAH1	XM_017006129.2	c.9433-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_016861618.1
DNAH1	XM_017006130.2	c.9364-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_016861619.1
DNAH1	XM_017006131.2	c.9433-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH1	ENST00000420323.7	c.9364-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_015512.5	ENSP00000401514	P1
DNAH1	ENST00000486752.5	n.9815C>T		non_coding_transcript_exon_variant	58/77	2
DNAH1	ENST00000488988.5	n.1144C>T		non_coding_transcript_exon_variant	6/25	2
DNAH1	ENST00000490713.5	c.64-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		5		ENSP00000419071

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 10, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.8
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00030
dbscSNV1_RF	Benign	0.0040
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

Publications

LitVar

Other links and lift over

dbSNP: rs1553641484; hg19: chr3-52422816;