rs776047200

Variant names:

• chr14-73654837-T-C
• rs776047200
• NM_031427.4:c.4-10T>C

Your query was ambiguous. Multiple possible variants found:

• chr14-73654837-T-C
• chr14-73654837-T-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_031427.4(DNAL1):​c.4-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000587 in 1,363,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: DNAL1 NM_031427.4 intron
• Scores: Splicing: ADA: 0.0004228
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 0 publications found

Genes affected

DNAL1 (HGNC:23247): (dynein axonemal light chain 1) This gene encodes an axonemal dynein light chain which functions as a component of the outer dynein arms complex. This complex acts as the molecular motor that provides the force to move cilia in an ATP-dependent manner. The encoded protein is expressed in tissues with motile cilia or flagella and may be involved in the movement of sperm flagella. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jan 2011]

DNAL1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 16

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAL1	NM_031427.4	c.4-10T>C		intron_variant	Intron 1 of 7	ENST00000553645.7	NP_113615.2
DNAL1	NM_001201366.2	c.-114-10T>C		intron_variant	Intron 2 of 8		NP_001188295.1
DNAL1	XM_017021679.3	c.-114-10T>C		intron_variant	Intron 2 of 8		XP_016877168.1
DNAL1	XM_024449715.2	c.-114-10T>C		intron_variant	Intron 2 of 8		XP_024305483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAL1	ENST00000553645.7	c.4-10T>C		intron_variant	Intron 1 of 7	1	NM_031427.4	ENSP00000452037.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000808 AC: 1 AN: 123780 AF XY: 0.0000152

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000194

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000587 AC: 8 AN: 1363552 Hom.: 0 Cov.: 33 AF XY: 0.00000595 AC XY: 4 AN XY: 672212

African (AFR) AF: 0.00 AC: 0 AN: 29166

American (AMR) AF: 0.00 AC: 0 AN: 26580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24056

East Asian (EAS) AF: 0.00 AC: 0 AN: 35562

South Asian (SAS) AF: 0.00 AC: 0 AN: 72458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5366

European-Non Finnish (NFE) AF: 0.00000747 AC: 8 AN: 1070604

Other (OTH) AF: 0.00 AC: 0 AN: 56464

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.60
PhyloP100		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00042
dbscSNV1_RF	Benign	0.0080
SpliceAI score (max)		0.010		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: rs776047200; hg19: chr14-74121540;