1-44806281-C-A

Variant names:

• chr1-44806281-C-A
• rs17884489
• NM_001377534.1:c.388G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001377534.1(DYNLT4):​c.388G>T​(p.Ala130Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000498 in 1,485,284 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00052 (10 hom.)
• Consequence: DYNLT4 NM_001377534.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.203
• Publications: 1 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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012619406).
• BS2: High Homozygotes in GnomAdExome4 at 10 gene

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.388G>T	p.Ala130Ser	missense	Exon 3 of 3	NP_001364463.1	Q5JR98
	DYNLT4	NM_001013632.4		c.388G>T	p.Ala130Ser	missense	Exon 2 of 2	NP_001013654.1	Q5JR98
	DYNLT4	NM_001377535.1		c.388G>T	p.Ala130Ser	missense	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.388G>T	p.Ala130Ser	missense	Exon 3 of 3	ENSP00000341803.2	Q5JR98
	DYNLT4	ENST00000675259.1		c.388G>T	p.Ala130Ser	missense	Exon 2 of 2	ENSP00000501642.1	Q5JR98
	DYNLT4	ENST00000854447.1		c.388G>T	p.Ala130Ser	missense	Exon 3 of 3	ENSP00000524506.1

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152124 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00848

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00169 AC: 150 AN: 88570 AF XY: 0.00199

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000620

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000252

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000713

GnomAD4 exome AF: 0.000522 AC: 696 AN: 1333052 Hom.: 10 Cov.: 32 AF XY: 0.000739 AC XY: 483 AN XY: 653964

African (AFR) AF: 0.0000707 AC: 2 AN: 28304

American (AMR) AF: 0.0000363 AC: 1 AN: 27564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22368

East Asian (EAS) AF: 0.0000298 AC: 1 AN: 33540

South Asian (SAS) AF: 0.00894 AC: 646 AN: 72276

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34220

Middle Eastern (MID) AF: 0.000205 AC: 1 AN: 4870

European-Non Finnish (NFE) AF: 0.00000474 AC: 5 AN: 1054518

Other (OTH) AF: 0.000722 AC: 40 AN: 55392

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152232 Hom.: 1 Cov.: 33 AF XY: 0.000363 AC XY: 27 AN XY: 74424

African (AFR) AF: 0.0000481 AC: 2 AN: 41576

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00849 AC: 41 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67972

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000430 Hom.: 0

Bravo AF: 0.0000982

ExAC AF: 0.00102 AC: 82

Asia WGS AF: 0.00406 AC: 14 AN: 3460

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.20
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.099
Sift	Benign	0.031	D
Sift4G	Uncertain	0.055	T
Polyphen		0.77	P
Vest4		0.34
MutPred		0.60		Gain of glycosylation at A130 (P = 0.0101)
MVP		0.15
ClinPred		0.052	T
GERP RS		4.6
Varity_R		0.066
gMVP		0.18
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs17884489; hg19: chr1-45271953;