1-44806105-G-A

Variant names:

• chr1-44806105-G-A
• rs1295444173
• NM_001377534.1:c.564C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001377534.1(DYNLT4):​c.564C>T​(p.Ser188Ser) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DYNLT4 NM_001377534.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68
• Publications: 0 publications found

Genes affected

DYNLT4 (HGNC:32315): (dynein light chain Tctex-type 4) Enables protein phosphatase 1 binding activity. Predicted to be involved in microtubule-based movement. Located in acrosomal vesicle; cytoskeleton; and sperm flagellum. [provided by Alliance of Genome Resources, Apr 2022]

PLK3 (HGNC:2154): (polo like kinase 3) The protein encoded by this gene is a member of the highly conserved polo-like kinase family of serine/threonine kinases. Members of this family are characterized by an amino-terminal kinase domain and a carboxy-terminal bipartite polo box domain that functions as a substrate-binding motif and a cellular localization signal. Polo-like kinases are important regulators of cell cycle progression. This gene has also been implicated in stress responses and double-strand break repair. In human cell lines, this protein is reported to associate with centrosomes in a microtubule-dependent manner, and during mitosis, the protein becomes localized to the mitotic apparatus. Expression of a kinase-defective mutant results in abnormal cell morphology caused by changes in microtubule dynamics and mitotic arrest followed by apoptosis. [provided by RefSeq, Sep 2015]

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=-0.65).
• BP7: Synonymous conserved (PhyloP=1.68 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377534.1. 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
	DYNLT4	NM_001377534.1	MANE Select	c.564C>T	p.Ser188Ser	synonymous	Exon 3 of 3	NP_001364463.1	Q5JR98
	DYNLT4	NM_001013632.4		c.564C>T	p.Ser188Ser	synonymous	Exon 2 of 2	NP_001013654.1	Q5JR98
	DYNLT4	NM_001377535.1		c.564C>T	p.Ser188Ser	synonymous	Exon 3 of 3	NP_001364464.1	Q5JR98

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNLT4	ENST00000339355.3	TSL:6 MANE Select	c.564C>T	p.Ser188Ser	synonymous	Exon 3 of 3	ENSP00000341803.2	Q5JR98
	DYNLT4	ENST00000675259.1		c.564C>T	p.Ser188Ser	synonymous	Exon 2 of 2	ENSP00000501642.1	Q5JR98
	DYNLT4	ENST00000854447.1		c.564C>T	p.Ser188Ser	synonymous	Exon 3 of 3	ENSP00000524506.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 233604 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1456264 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724172

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 44180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25910

East Asian (EAS) AF: 0.00 AC: 0 AN: 39528

South Asian (SAS) AF: 0.00 AC: 0 AN: 85664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110124

Other (OTH) AF: 0.00 AC: 0 AN: 60114

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.9
DANN	Benign	0.86
PhyloP100		1.7
Mutation Taster		=99/1	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: rs1295444173; hg19: chr1-45271777;