rs738144

Variant names:

• chr22-38782370-G-A
• rs738144
• NM_005740.3:c.69+293C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-38782370-G-A
• chr22-38782370-G-C
• chr22-38782370-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005740.3(DNAL4):​c.69+293C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 152,228 control chromosomes in the GnomAD database, including 53,502 homozygotes. 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: 𝑓 0.84 (53502 hom., cov: 35)
• Consequence: DNAL4 NM_005740.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 8 publications found

Genes affected

DNAL4 (HGNC:2955): (dynein axonemal light chain 4) 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. [provided by RefSeq, Dec 2014]

SUN2 (HGNC:14210): (Sad1 and UNC84 domain containing 2) SUN1 (MIM 607723) and SUN2 are inner nuclear membrane (INM) proteins that play a major role in nuclear-cytoplasmic connection by formation of a 'bridge' across the nuclear envelope, known as the LINC complex, via interaction with the conserved luminal KASH domain of nesprins (e.g., SYNE1; MIM 608441) located in the outer nuclear membrane (ONM). The LINC complex provides a direct connection between the nuclear lamina and the cytoskeleton, which contributes to nuclear positioning and cellular rigidity (summary by Haque et al., 2010 [PubMed 19933576]).[supplied by OMIM, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAL4	NM_005740.3	c.69+293C>T		intron_variant	Intron 2 of 3	ENST00000216068.9	NP_005731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAL4	ENST00000216068.9	c.69+293C>T		intron_variant	Intron 2 of 3	1	NM_005740.3	ENSP00000216068.4
SUN2	ENST00000406622.5	c.-138+11698C>T		intron_variant	Intron 1 of 18	2		ENSP00000383992.1
DNAL4	ENST00000406199.3	c.69+293C>T		intron_variant	Intron 2 of 2	2		ENSP00000385712.3
DNAL4	ENST00000486019.1	n.82-2757C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.838 AC: 127415 AN: 152110 Hom.: 53447 Cov.: 35

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.829

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.838 AC: 127529 AN: 152228 Hom.: 53502 Cov.: 35 AF XY: 0.837 AC XY: 62280 AN XY: 74430

African (AFR) AF: 0.859 AC: 35682 AN: 41560

American (AMR) AF: 0.874 AC: 13364 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.798 AC: 2769 AN: 3468

East Asian (EAS) AF: 0.890 AC: 4616 AN: 5188

South Asian (SAS) AF: 0.831 AC: 4016 AN: 4830

European-Finnish (FIN) AF: 0.794 AC: 8392 AN: 10574

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.825 AC: 56065 AN: 67998

Other (OTH) AF: 0.831 AC: 1756 AN: 2114

Alfa AF: 0.840 Hom.: 32179

Bravo AF: 0.844

Asia WGS AF: 0.878 AC: 3054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.082
DANN	Benign	0.68
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs738144; hg19: chr22-39178375;